The England and United captain's straight red card in last Saturday 2-1 win over West Ham United will mean Louis van Gaal will have a bit of tinkering to do.
United aren't short of options in Rooney's position, sitting just behind Robin van Persie and Falcao. Three men who will be desperate for the chance to prove themselves in the skipper's absence are Juan Mata, Adnan Januzaj and Marouane Fellaini.
All of the trio could be in line to make the match day squad for United's tricky trip to Everton this Sunday, but only one of them can fill Rooney's shoes. Who will it be?
Probably the most likely of the three is Spanish playmaker Juan Mata. Signed from Chelsea last January for £37.1 million, Mata brought a new air of confidence around United last season and his immediate impact was very good.
In the fifteen league games Mata featured in last season he scored six and assisted a further four. His form this season though hasn't been as impressive with two goals and zero assists in five appearances. Also despite his pass success rate being higher than last season, his number of key passes per game has been far too low for someone in his position, as are his shots and successful dribbles.
The 26-year-old will be desperate to prove he's still an important figure at United especially as the arrival of Angel Di Maria and Falcao has raised questions over his long-term future at the club.
It will be a year to the day on Sunday since Belgian sensation Adnan Januzaj scored two goals on his first ever start for United against Sunderland. The 19-year-old was the highlight of an otherwise miserable season for United under Moyes, but hasn't had as many chances under Van Gaal as of yet.
Januzaj has talent, that's undeniable. Despite his end product not yet being up to scratch he shows glimpses of brilliance in almost every game he plays in.
He been dropped back down to the under-21s for game-time recently, but has showed he's more than good enough to feature regularly in the United first team. A hat-trick against Sunderland u21s in front of the onlooking United boss, and then a sublime free-kick against a young Spurs side would have done his chances the world of good.
Arguably the most unlikely of the three to take the Rooney spot is Belgian giant Maraoune Fellaini. The midfielder had a first season to forget for United and was reportedly close to departing over the summer, but somehow ended up surviving the cull.
He showed during his Everton days that he is adept at playing behind the striker, so long as the team plays around him. In the 2012/13 season he was lethal for the Toffees as an advanced midfielder, he held the ball up, bullied defenders and scored goals. Unfortunately as of this moment, he hasn't been anything like that sort of player for United.
If Fellaini does feature against his old club Van Gaal would more most likely drop him into a three man midfield, sitting behind the two forwards and in front of the holding Daley Blind.