Though it was initially unclear if Fellaini had been injured, United boss Jose Mourinho confirmed after the match that the Belgian had suffered a knee issue during his time on the pitch.
With his side down 2-0 in the 63rd minute, Mourinho introduced Fellaini in place of Jesse Lingard.
But, just seven minutes later, Fellaini was substituted himself, with Ander Herrera introduced by Mourinho.
Fellaini walked off the pitch and straight down the tunnel after being taken off.
Following the match, Mourinho confirmed that the Belgian had suffered an injury during his brief time on the pitch.
"He came off because he had something in his knee," Mourinho told BBC's Match of the Day.
"Unlucky for him and unlucky for me. He came on with enthusiasm, but he has an injury in his ligament."
United went down 1-0 at Wembley within just 11 seconds, as Christian Eriksen scored one of the fastest goals in Premier League history.
And it would get worse for United later in the first half, with Phil Jones scoring an own goal to make it 2-0.
Spurs would go on to win the match 2-0 after a scoreless second half, moving to within two points of the top four after Chelsea's surprise defeat against Bournemouth.