The young Red Devils are facing tough competition in the group stages, going up against more experienced senior teams.
These matches are a useful way for young players to understand the senior game.
While United fell behind in the contest, they roared back to beat Barnsley 3-2 on the night. Jack Fletcher scored twice, with Ethan Ennis also netting for United.
Manchester City Under-21s drew 1-1 at Chesterfield, while Tottenham Under-21s drew 3-3 against Bristol Rovers.
Lower league Burton Albion came from behind to beat Leicester City Under-21s 3-1.