Sir Alex Ferguson reacted to Wednesday's shock 1-0 loss at promoted Burnley by making seven changes and the United manager was rewarded with a superb second half display.
It took the revamped United line-up a while to find their rhythm but, after a goalless first half, Rooney struck in the 56th minute when he met a cross from former Wigan winger Antonio Valenica with a perfect header.
That was Rooney's 100th goal for United and it opened the floodgates.
Dimitar Berbatov put United in complete control in the 58th minute. The Bulgarian finished a flowing move by chipping over Chris Kirkland and shooting into an empty net.
Rooney ended any doubts about the result in the 65th minute when his shot deflected off Mario Melchiot and flashed past the wrong-footed Kirkland.
Owen, signed from Newcastle in the close-season, came off the bench to score for the first time since January with a sublime clipped finish.
Nani, who set up Owen's goal, got on the scoresheet himself in the 90th minute.
"You have to react to a defeat, that's always the challenge," Ferguson said. "We got a reaction, I thought our performance was really good.
"It's great for Wayne to get 100 goals. He's only a young lad and there are players who have been here longer who have got nowhere near that total.
"I'm pleased for Michael as well. He needed a goal, but he's one of the best finishers our country has had."
Arsenal maintained their impressive start to the season with a 4-1 victory over struggling Portsmouth at the Emirates Stadium that sent them top of the table.
The Gunners had confounded critics who wrote off their title hopes by thrashing Everton 6-1 last weekend, then winning at Celtic in the Champions League in midweek.
Wenger still made four changes to the side that beat Celtic, but it proved a successful move as French midfielder Abou Diaby, brought into the team for his 100th Arsenal appearance, opened the scoring in the 18th minute from Eduardo's pass.
Diaby converted Emmanuel Eboue's cross for his second goal three minutes later but Portsmouth reduced the deficit when Younes Kaboul, out-jumping keeper Manuel Almunia, headed home in the 37th minute.
Any hopes of a fightback from Paul Hart's team were ended in the 51st minute through William Gallas's scrambled effort.
Aaron Ramsey confirmed Portsmouth's third successive defeat in the 68th minute with his first league goal for Wenger's team.
"We have had a brilliant start. It should create confidence and momentum," Wenger said.
"We now go into another week which will be another test against Celtic and then Manchester United. It looks to be exciting and interesting."
Manchester City striker Emmanuel Adebayor repaid another slice of his 25 million pounds transfer fee as the Togo star's cool finish sealed a 1-0 win over Wolverhampton at Eastlands.
City handed Carlos Tevez his full debut and the former Manchester United forward's cushioned 17th-minute pass picked out Adebayor, who drove in his second goal in two games since joining City from Arsenal.
Trinidad and Tobago forward Kenwyne Jones fired Sunderland to a 2-1 victory over Blackburn.
Sam Allardyce's Rovers, without defender Stephen Warnock as rumours of a move to Aston Villa gathered momentum, took the lead in the 21st minute when French defender Gael Givet smashed a long-range effort past Marton Fulop.
But Sunderland equalised after 32 minutes as Jones took advantage of a slip by Christopher Samba to slot home.
Jones wasn't finished there. In the 53rd minute he met Lee Cattermole's cross with a bullet header to seal the points for Steve Bruce's team.
Hull won for the first time in 13 league matches as Algeria striker Kamel Ghilas's first goal for the club earned a 1-0 victory over Bolton at the KC Stadium.
Ghilas was making his first start for the Tigers after signing from Spanish club Celta Vigo earlier this month.
He marked the occasion in the 61st minute with a blistering volley from Jozy Altidore's pass.
Stoke recovered from their midweek thrashing by Liverpool by grinding out a 0-0 draw at Birmingham.