Spurs visit Old Trafford for the Premier League clash in Jose Mourinho's first return to the club since he was fired in December last year.
Per Sam Carney of United's official website, James said of the match:
"Yeah, I think it's massive. Obviously, we go into every game wanting to win, but I think the midweek games, especially under floodlights, are massive.
"The fans are going to be right behind us, but it's a massively important game and we want to go into that with our heads held high and hoping that we can win."
Referring to United's 1-1 draw with Liverpool in October, James added that good performances in big matches such as those "give you a great step going forward."
The Red Devils have not been in good form since they returned from the international break:
The results have left them 10th in the Premier League having won just four of 14 games this season. They're 22 points behind leaders Liverpool and eight off the top four.
BBC Sport's Simon Stone put their position in further damning context:
Football writer Liam Canning was disappointed with how they performed against Aston Villa on Sunday:
A win on Wednesday would send them ahead of Spurs and potentially to fifth place, though. It would also be a timely morale boost ahead of United's visit to Manchester City on Saturday.
They'll also be playing AZ Alkmaar in the UEFA Europa League and Colchester United in the Carabao Cup quarter-final, so keeping momentum throughout the month might be difficult. If they're to have any chance of reeling in the top four, they need to take advantage of the busy period to gain ground.
The Red Devils have won five of Spurs' last six visits to Old Trafford in all competitions, but the Lilywhites recorded a 3-0 victory there in the most recent of those.
Spurs have scored 10 goals in Mourinho's first three games in charge, but they've also conceded twice in each of them. United have scored 12 in their last five and shipped eight in that time, so there could be plenty of goals in Wednesday's clash.