Robin van Persie marked his first Manchester United start with a sublime goal, but his side's 3-2 victory over Fulham was marred by a nasty injury to Wayne Rooney that will sideline the England striker for four weeks.
Van Persie had little chance to contribute during a brief substitute appearance in United's lacklustre defeat at Everton on Monday, but took just 10 minutes to make his mark at Old Trafford with a brilliant half-volley to cancel out Damien Duff's opener.
Inspired by the Dutch striker, United went on to secure their first win of the season.
But the result was overshadowed by Rooney's injury late in the second half, which left the England striker, who was stretchered off, with blood streaming from a deep gash in his thigh after he was caught by Hugo Rodallega.
Rooney was taken to hospital for treatment and United coach Sir Alex Ferguson said he will be out for four weeks.
Fulham had stunned United when Irish winger Duff fired home from just inside the penalty area in the third minute.
But that brought a scintillating response from van Persie, who levelled with a blistering strike from Patrice Evra's cross.
Like van Persie, Shinji Kagawa was making his first appearance at Old Trafford and he marked the occasion by tapping in his maiden United goal.
United defender Rafael da Silva added a third goal in the 41st minute before Nemanja Vidic's 64th-minute own goal gave Fulham a glimmer of hope.
While United are off the mark, it is Chelsea who are setting the early pace as the European champions cemented their position on top of the table with a 2-0 win against Newcastle United at Stamford Bridge.
Roberto Di Matteo's side, who have recorded three successive victories, went ahead in the 22nd minute when Eden Hazard drilled home his first Chelsea goal from the penalty spot after a Vurnon Anita foul on Fernando Torres.
Spain striker Torres added the second goal himself, lashing in from Hazard's back-heel just before half-time.
Everton, often hampered by slow starts to the season, also maintained their 100 per cent record with a 3-1 win over 10-man Aston Villa.
South Africa midfielder Steven Pienaar gave David Moyes' side the perfect start as he struck in the third minute at Villa Park.
Marouane Fellaini increased the lead with a 31st-minute header and Croatia striker Nikica Jelavic swept home a Leighton Baines cross just before half-time.
Villa defender Ciaran Clark earned a straight red card for a professional foul on Jelavic in the second half and Karim El Ahmadi's 74th-minute goal was little consolation for the hosts.
Andre Villas-Boas was denied a first win as Tottenham Hotspur manager as James Morrison's late goal secured a 1-1 draw for West Bromwich Albion at White Hart Lane.
Benoit Assou-Ekotto struck for Tottenham in the 74th minute with a deflected shot, but Steve Clarke's side levelled through Morrison in stoppage time.
"It is very important to get that first win but there are still 36 games ahead of us," Villas-Boas said.
Norwich City and QPR, both thrashed 5-0 last weekend, shared the spoils in a 1-1 draw at Carrow Road.
Wigan Athletic won 2-0 at Southampton, while Sunderland's match against Reading was postponed less than 90 minutes before kick-off due to a waterlogged pitch.