After a goalless first leg in Spain last month, the Red Devils were expected to take the game to their visitors to avoid the possible sucker-punch of an away goal.
However, the aggregate deadlock remained intact 164 minutes into the tie, and was only broken by Sevilla substitute Wissam Ben Yedder 88 seconds after his introduction.
The Moroccan striker bagged another four minutes later and although United pulled one back through Romelu Lukaku six minutes from time, it was too little, too late.
Relive how the action unfolded in Manchester with our minute-by-minute updates below.
6.45pmThe big games come thick and fast at this stage of the season, and after beating Liverpool in the Premier League on Saturday, Manchester United aim to join their fierce rivals in the last eight of the Champions League, but must first overcome Sevilla with the scores deadlocked at 0-0 from the first leg.
6.47pmBecause of United's failure to score in Spain last month, or more appropriately their willingness not to try, this tie is finely poised ahead of tonight's second leg. An away goal for Sevilla would leave United needing to score two, which they haven't done in their last 15 games with La Liga opposition.
6.53pmPaul Pogba is back on the United bench after missing this weekend's win over Liverpool, but Mourinho chooses not to start the Frenchman and instead hands Marouane Fellaini a first start since Novemebr, signalling his faith in the Belgian midfielder. Scott McTominay drops out of the XI.
6.55pmAfter his brilliant two-goal haul against their Merseyside foes, Marcus Rashford earns back-to-back starts as he is preferred to Juan Mata and Anthony Martial, who is named among the substitutes after missing the last two matches. The Frenchman has been a super sub for United last season.
6.57pmJesse Lingard is recalled as Mourinho goes with a 4-2-3-1 formation, as opposed to the more conservative three-man midfield that the Special One fielded in the first leg. United need to take the attack to Sevilla in the first half, as they did with Liverpool, otherwise this could get sticky in the second.
6.59pmEric Bailly emerged from his first start in three months unscathed to play again at centre-back this evening, which is a relief with Mourinho's options there limited by injuries to Phil Jones and Marcos Rojo. Ander Herrera, who started in the first leg, and Daley Blind, are also unavailable for United.
7.01pmSevilla are without defenders Sebastien Corchia and Daniel Carrico, who failed a late fitness test Ex-Manchester City winger Jesus Navas is still nursing an injury and does not make the squad.
7.03pmVisiting manager Vincenzo Montella has signalled his intention to perform a Mourinho-esque smash-and-grab on United by leaving out top scorer Wissam Ben Yedder, who has 15 goals for the season including eight in the Champions League. Luis Muriel starts as the lone striker again.
7.05pmMuriel was guilty of missing a golden chance for Sevilla in the first leg. Here is a reminder of the brilliant David de Gea save that denied the striker and kept the tie goalless heading to Old Trafford.
Man Utd host Sevilla tonight in the return leg tonight...
7.07pmThere is only one change for to the Sevilla XI which started at the Ramon Sanchez Pizjuan, and again that is defensively minded with experienced defender Simon Kjaer in for Jesus Navas.
7.09pmJoaquin Correa is recalled as another former Man City player - Nolito - is axed from the team which lost 2-0 to Valencia on Saturday, their second defeat in four matches since the first leg.
7.11pmSTAT: Something which nervy United fans can lean on here; 70% of away sides who draw the first leg of a Champions League knockout tie 0-0 end up progressing to the next round.
7.13pmUnited have an excellent record against Spanish sides at Old Trafford, having only lost one of their past nine home Champions League games - against Real Madrid at this stage in 2012-13.
7.15pmHowever, it is usually low scoring when the Red Devils face La Liga opponents, and that might favour Sevilla in this instance if they can find an away goal. United have only bagged seven goals in 15 previous matches against Spanish sides, failing to score more than once in a single one of those games.
7.17pmSpanish sides are Mourinho's kryptonite in the Champions League. Five of his seven losses, in a total of 69 Champions League home games as manager, have been against teams from La Liga.
7.19pmWhen a Spanish side does not get in his way, there is no doubt that the Special One knows how to get things done in Europe. In 11 full seasons as manager in the Champions League, Mourinho has reached the quarter-finals eight times, falling only at this stage in 2005-06, 2008-09 and 2014-15.
7.21pmUnited are due a run deep into the Champions League, having struggled in the late Sir Alex Ferguson era. Since the 2011 final, United have won only one of their past eight knockout games, although this is the first year that they have reached the knockout stages of the competition in four years.
7.23pmTheir outstanding home record should give the Red Devils confidence that they can get the job done tonight - they have won 15 of their 18 home games so far in all competitions this season.
7.25pmTheir defensive record has been the secret to United's Old Trafford fortress. Only Barcelona (two) have conceded fewer goals in this season's Champions League than United's three.
7.27pmIn contrast, Sevilla have the second worst defensive record of those teams remaining in the competition. Only Porto (15) have let in more than Sevilla's 12, with five apiece coming against Liverpool although the Spaniards did restrict Jurgen Klopp's side to draws in each of their two group games.
7.29pmTheir 2-2 draw at Anfield in September is the only time that Sevilla have visited England and avoided defeat in Europe's top club competition, losing their other three Champions League matches.
7.31pmHowever, it has not just been in England that Sevilla have struggled on their Champions League travels. After winning four of their first six away games in the competition, Los Rojiblancos have picked up just one win in their past 12 games on the road.
7.33pmWhat the first-leg stalemate does is make the formula for United tonight pretty simple - win and they are through. A draw, unless it is another 0-0 and thus extra time and penalties, won't be enough.
7.35pmA reminder of which teams have already booked their passage to the quarter finals - Real Madrid, Manchester City, Juventus and Liverpool - so the last-eight draw is already looking tasty!
7.37pmRoma and Shakhtar Donetsk also settle their last-16 tie, with the Ukranian outfit 2-1 up aggregate. I will keep you up to date on the score from the Italian capital, and the rest of the Champions League sides will be keeping an eye on that tie too as it will produce arguably the easiest last-eight opponent.
7.39pmDe Gea was the first-leg hero and his Champions League form this season has been amazing...
20 - David de Gea has saved 20/21 opposition shots that he's faced in the Champions League this season. He has only conceded one goal but Opta xG data suggests that the average goalkeeper would have conceded five goals from these shots. Superhuman. #MUNSEVpic.twitter.com/e1WRAj5HvA
7.41pmLess than five minutes until kickoff now, as the players emerge from the tunnel. Thankfully Fellaini is sporting his usual afro rather than this atrocity that he experimented with in Belgium's World Cup marketing campaign.
7.43pmPREDICTION: It has been four years since David Moyes took United to the Champions League quarter-finals, and I think that wait will end tonight. United's home record is mightily impressive and that front four should be enough to steer the hosts to a 2-0 victory.
1 minKICKOFF: Sevilla get the action underway, on their first ever competitive visit to Old Trafford...
2 minUnited release Lukaku early down the left and he bullies Kjaer off the ball before cutting inside and playing a one-two with Lingard. The subsequent right-footed shot is high and out of control.
4 minRashford has started on the right wing, with Sanchez on the left and Lingard as the No.10. The two-goal hero from Saturday shifts and shoots but Sergio Escudero gets a vital block in.
6 minYELLOW! Ever Banega is Sevilla's creative force in midfield but a couple of times already he has been robbed by Fellaini, and the Argentine's frustration causes him to jump in on Sanchez with a late slide tackle which earns him a deserved yellow card.
8 minA careless pass out of defence from Valencia gifts the ball to Escudero, who should have picked out Muriel with a simple through-ball but wastes what was a promising opening for the visitors.
10 minCLOSE! Banega swings a lovely corner into the near post and Correa made a run across Matic to win the header, glancing it just over the crossbar and onto the roof of the net.
12 minSevilla have had lots of the ball in the last five minutes and have quickly quietened the Old Trafford crowd. The ball breaks to Vasquez but Bailly stretches out a leg to block his low shot.
14 minCHANCE! Bailly criminally gives the ball away in front of his own area and Sevilla work it to Muriel, who snatches at his first-time shot to let the Ivorian defender of the hook.
16 minN'Zonzi, once of Blackburn and Stoke of course, picks out a really good pass in between the lines, and Muriel tees up Vasquez for a shot which ends up deep in the Stretford End.
18 minMourinho may be a little concerned by his side's start, which is a million miles away from the high-tempo of the Liverpool game. Sevilla have taken control of the game and had their mid-range shooting been a little more accurate then they might have really put the cat among the pidgeons.
20 minRashford and Lingard are being forced to drop into their own half to get possession, with Fellaini occupying a position just behind Lukaku when United have the ball. Their only success so far is when they have gone direct to one of the two big men, which is hardly 'the United way'.
22 minOn the Sevilla left, Correa looks like a tidy player. He has not long established himsef as a first-team regular but the 23-year-old looks to be the ball that the visitors are looking to most often.
25 minSanchez finally gets himself involved, cutting in from the left and whipping a deep cross towards the back post where Escudero heads behind under pressure from Rashford. Old Trafford rises...
27 minSHOT! Sarabia and Vasquez exchange flicks in the United half before the former releases Muriel down the left channel. The angle is against him as he shoots left footed across goal and wide, with De Gea unconcerned which is not how most United fans will feel right now.
29 minRashford knocks a ball over the top for Lukaku, but Clement Lenglet does just enough to put the Belgian off and prevent him from bringing the ball under his control on the penalty spot.
31 minThe England forward is trying to get the Red Devils going here, skipping past two Sevilla players while bursting down the left only for Lenglet to come across and stop him in his tracks.
33 minOne of United's best moves of the match so far starts with Lukaku dropping to the halfway line and switching the play to Young. Fellaini's knockdown at the back post falls to a Sevilla defender.
34 minSHOT! We've had our first shot on target of the game, but it is a very tame one from Muriel which De Gea collects with ease. His toothlessness could cost Sevilla this tie.
36 minA Kjaer clearance falls at the feet of Sanchez, who drops his shoulder to lose Sarrabia but then gets caught in two minds with a cross-cum-shot which Rico comes off his line to collect.
38 minSAVE! The hosts finally create something as Sevilla switch off while appealing for a foul on Banega by Fellaini, who plays a tight one-two with Sanchez and thrashes a left-footed shot towards the near post which Rico pushes away.
40 minYoung has bags of time and space to swing in a cross from the left, but he waits too long and Mercardo, playing slightly out of position at right back, closes him down to block the cross. The second ball falls to Fellaini whose own effort hits a Sevilla defender. United are building a little momentum here...
42 minA well-judged return pass from Rashford sets Lingard free to the right byline. He fizzes a cross in towards the near post which the so-far excellent Lenglet clears off the toe of Lukaku.
44 minA lack of conviction lets Muriel down again as he underhits a simple pass to the overlapping Correa, who would have been through on De Gea's goal had the poor pass not allowed Valencia to nip in.
8.34pmTwo hours and 15 minutes into this tie and we are still goalless, and in truth it has been Sevilla who have looked the more likely to change that in the opening half at Old Trafford. United got out of first gear towards the end of the half but as it stands we would be heading to extra time.
8.36pmAfter coming out positively against Liverpool and winning, it is strange that United have gone back into their shell tonight. They clearly have the attacking talent to take the game to Sevilla and score the goals to put them to bed, but fear has most definitely conquered ambition so far.
8.38pmThis sums up the first half pretty well, although it has occasionally finished with a long punt to Fellaini...
Smalling to Bailly .. passes back to Smalling who passes back to Bailly .. Ashley Young with the ball now .. back to Smalling .. back to Bailly who passes back to Smalling .. back to De Gea who rolls it back to Bailly who finishes with a great pass to Smalling 💤💤... #MUNSEV
8.40pmLATEST: It is also 0-0 in tonight's other Champions League game, but Shakhtar Donetsk's 2-1 first-leg victory in Ukraine would currently see them through against Roma.
8.42pmSTATS: There has been an equal 50% share of possession so far although neither side has managed to convert that into more than one shot on target. A United side which includes Sanchez, Rashford and Lukaku should be doing better than that. Sevilla have more of an excuse...
8.44pmBENCH WATCH: Juan Mata had a big impact coming off the bench when United came from behind to beat Crystal Palace last week. Mourinho also has Anthony Martial at his disposal but might feel that it is a bit early to play that card. Of course, there is Paul Pogba too...
46 minKICKOFF: The action resumes with both sides unchanged. Mourinho looks pretty calm on the bench but the longer that this tie stays goalless the more anxious Old Trafford will get.
48 minCHANCE! Bailly has just made a tackle which might keep United in the Champions League! The hosts get caught out and leave Correa in acres of space in the box but when the Argentine turns to try to get a shot away from 12 yards, Bailly rescues his side with a perfectly-timed slide.
50 minSevilla have defended set pieces very well so far tonight, and that may have been an area that United hoped to explot with Fellaini in the team, as well as Lukaku, Matic and Smalling.
52 minSAVE! Better from United as Lingard creates space for a low shot across goal which Rico does very well to push away diving to his right. Rashford recycles possession and works his way to the byline, from where he drills the ball across goal but no United player was willing to gamble.
53 minCorrea weaves his way into the box before poking a shot harmlessly wide. The South American looks very graceful when he's on the ball but so far an end product has been lacking.
55 minSanchez spreads the ball out to Rashford on the right, but his inexperience shows as he delivers a ball too early and too deep for Lukaku, who was the only United player in the area.
57 minCHANCES! Rashford dribbles into the box, staying on his feet in spite of an Escudero foul, and lays the ball off for Sanchez, who can't get it out of his feet and eventually prods the ball goalwards with Lenglet making a crucial block.
At the other end Sevilla work it nicely to Sarrabia on the right wing, and his cross could easily have been turned past De Gea by either Muriel or Bailly as they duelled at the near post.
59 minSUBSTITUTION: Mourinho makes his first move, swapping Fellaini for Pogba in midfield. Now would be a fantastic time for the £87m signing to answer some of his recent critics.
61 minSanchez drops a cute ball over the Sevilla defence for Lukaku to battle for. He gets in front of Lenglet and shoots left footed as the ball drops, but the defender gets another block in.
64 minSevilla might well lead this tie had they had one of their strikers of the past, such as Luis Fabiano or Alvaro Negredo. Their build-up play is often very good but their finishing very poor.
66 minRashford has moved over to the left and he skips past Mercardo and Sarrabia before being bundled to ground by both of them. This is a really good free-kick opportunity for the hosts.
67 minThe United youngster tries to whip a shot into the far top corner but gets it badly wrong.
69 minAnother poor set piece, this time from Sarabia for Sevilla as he knocks a cross beyond all of his teammates and behind for a goal kick. Could I double check this is the last 16 of the Champions League?!
71 minThe Old Trafford crowd are restless as they chant "attack, attack, attack." Rashford responds with a rapid burst down the left but his cross is cleared by the flawless Lenglet in the six-yard box.
72 minSHOT! Pogba tries to pick his spot with a left-footed curler from 25 yards, which has goalkeeper Rico scrambling across his goal but goes just wide of the post.
74 minGOAL! MANCHESTER UNITED 0-1 SEVILLA (WISSAM BEN YEDDER)
74 minManchester United are in deep trouble now as Wissam Ben Yedder finally breaks the deadlock, two minutes after coming on as a substitute! Banega and Sarabia have too much space to move the ball forward, and the striker escapes Bailly to rifle a shot into the bottom corner past De Gea.
76 minTo be clear, United now need two goals in 15 minutes to make the quarter-finals. One goal won't be enough as Sevilla would go through on away goals. It is a lot to ask for them to suddenly pour forward seeing as though the approach has been so cautious across both of the two matches.
77 minSUBSTITUTIONS: Mourinho responds with a double change, bringing on Martial and Mata for Lingard and Valencia.
78 minGOAL! MANCHESTER UNITED 0-2 SEVILLA (WISSAM BEN YEDDER)
78 minThe Red Devils, the three-time European champions, are crashing out of the Champions League. Correa is allowed a free header at the near post and his flick on reaches Ben Yedder, who steers the ball underneath the crossbar. De Gea pushes it onto the woodwork but it bounces down and over the line.
9.43pmMajor disappointment for United as they fail to take advantage of a friendly last-16 tie, with substitute Wissam Ben Yedder the second-half hero for Sevilla who reach the quarter-finals for the first time. Roma are also through to the last eight, progressing past Shakhtar Donetsk on away goals.
9.45pmIf United fans can stand it, give our match report on the action at Old Trafford here. That's it from me, but Sports Mole are back with minute-by-minute updates on tomorrow's Champions League ties. Hopefully Chelsea fare better than United did. Until then, thanks for joining us!