Spurs have played all of their home matches at the national stadium this season while construction continues on their new state-of-the-art ground across the capital.
Mourinho has rubbished talk that Tottenham have an advantage by playing in familiar surroundings, however, having had mixed fortunes in such situations in the past with Inter Milan and Real Madrid.
Speaking at his pre-match press conference, the Portuguese said: "I played one cup final in Roma's stadium against Roma [as Inter coach in 2010] and I won, and I played a cup final in my stadium [at the Santiago Bernabeu in 2013, as Real coach] and I lost, so I think, when you go to these big moments with big decisions, semi-finals, finals, I don't think it's an advantage at all.
"In some countries, even the cup semi-final is played with a draw and you play home or away, not at a neutral ground, and that's just football. I look at Tottenham-Manchester United the same way I looked at Huddersfield, or Brighton. This time it's away but I don't see any advantage. It's the same as playing at Old Trafford."
Man United and Tottenham have met in 10 previous FA Cup ties, progressing five times each.