The Red Devils, who will face Athletic Bilbao in the next round after winning the first leg away at Ajax 2-0, lost 2-1 at home in a game they very much should have won.
Especially after Javier Hernandez put them in front with just six minutes on the clock.
Tactically United were brilliant in the first half, and had many chances to kill the game off.
But when Aras Ozbiliz scored that sensational equaliser on 37 minutes, Ajax grew in confidence and carried their late momentum into the second period, where they executed Frank de Boer's tactics perfectly, leaving Sir Alex Ferguson's side unable to get a hold on the match or even just retain possession.
Here are five tactical observations on the game at Old Trafford.