Luis Alberto scored the only goal of the game as CFR Cluj stormed Old Trafford to escape with the biggest win in their history.
As expected, ahead of the Manchester derby this weekend, Sir Alex Ferguson made wholesale changes from the side that beat Reading at the weekend and his team paid the price on a low key night in the North West.
Truth be told they actually started brightly but found Mario Felgueiras in fine form between the sticks, as he denied Nick Powell and Javier Hernandez early on.
Cluj though looked dangerous on the break and could easily have scored in the 20th minute when Ryan Giggs' careless pass across his own goal ended with Chris Smalling deflecting Rui Pedro's shot goalwards but David De Gea reacted well to save.
The hosts pushed on as the half wore on and when Danny Welbeck's header was superbly saved before Wayne Rooney's delightful chip was palmed away by the keeper, the chance fell to Chris Smalling to head home from two yards out but he diverted the ball wide.
The second half was one of frustration for a quiet home crowd and their frustrations were only heightened when Alberto rattled in a swerving shot from 30 yards out that crashed in off the inside of the post just before the hour mark.
There were half chances for United after that but they just couldn't find the breakthrough, despite applying intense pressure in the final third.
The only dampener for the visitors was that they were eliminated from the Champions League by Galatasaray's victory in Braga so the Romanians will have to make do with the Europa League after Christmas.
Manchester United were already confirmed as group winners but, with City to come at the weekend, they will be hoping to have not lost any momentum and will need to improve for the knockout stages of this season's Champions League.