With the scoreline level at one apiece, Holding went down clutching his knee following a challenge from Marcus Rashford and immediately it looked as if he was some discomfort.
Its often a tell-tale sign when a visiting player is applauded off the pitch by the home supporters as the United faithful did when Holding made his way down to the dressing room on the stretcher.
Holding has enjoyed an excellent run in the Arsenal side, starting the last nine in the Premier League, but Emery virtually confirmed it would be his last outing for a while.
The worst news for us. Rob Holding we are going to wait for the doctors, but it is a big injury. Its his knee, Emery said after the game.
It was a bruising encounter all round for Arsenal with a number of players suffering knocks and niggles, including Aaron Ramsey who also had to be substituted in the first-half.
Emery had better news on the Welshman, though, saying: Aaron I think it is a small injury.
At one stage it looked as if Arsenal would struggle to see them game out with their full compliment of players as Lucas Torreira, Shkodran Mustafi and Alexandre Lacazette all suffered knocks in the second half.
Emery had better news over club captain Laurent Koscielny, saying: Laurent is very close. He played two matches for U23, including one on Tuesday. I dont know if Saturday is possible but Europa League match would be good for him.
Arsenal are next in action against Huddersfield Town at the Emirates on Saturday and Emery may well be tempted to rotate his side following a couple of bruising encounters over the last few days against Spurs and Manchester United.
More: Arsenal FC