Rooney made the breakthrough in the 56th minute and got his second nine minutes later in a fine second-half show.
In between, Dimitar Berbatov found the target in the 58th minute as United bounced back from their humbling by newly-promoted Burnley in midweek.
Owen made his mark in the 85th minute after replacing Rooney, and Nani completed the scoring in stoppage time with a superb free-kick.
The day, however, belonged to Rooney, such an unselfish worker, as he scored his 100th and 101st goals for the club.
Yet United found it hard going in the first half even though they had plenty of possession.
Manager Sir Alex Ferguson looked concerned at the break after making seven changes to his side in a bid for victory at the DW Stadium.
He was looking for an immediate response after what happened at Turf Moor and his side almost took the lead in the fourth minute with a swift break.
Nani cut the ball back into the area and Darren Fletcher was the first to react but saw his effort cleared off the line by Titus Bramble.
Three minutes later Paul Scholes hoisted a shot high over the crossbar following a clever flick from Berbatov after Fletcher had carved out the opening.
Wigan were again on the back foot after 16 minutes when Rooney strode forward but his effort was deflected wide.
Rooney then made time and space in the area only for goalkeeper Chris Kirkland to smother his close-range shot.
United were looking menacing every time they poured forward and Berbatov headed into Kirkland's arms following a cross from Nani four minutes later.
Wigan, however, almost took the lead with their first real attack in the 26th minute.
Jason Koumas showed good skill to work his way to the edge of the penalty area. He tried to curl the ball beyond Ben Foster only for the goalkeeper to react superbly and divert it to safety.
United responded in the 32nd minute and Rooney got away from Bramble only to rattle a shot against Kirkland's legs.
Then Fletcher's effort was cleared in the 39th minute after he had been set-up by Scholes.
Wigan, however, came close to opening the scoring in the 49th minute when Charles N'Zogbia won a free-kick off Patrice Evra early in the second half.
N'Zogbia dusted himself down and and picked out Paul Scharner in the area. He peeled away from his marker only to head narrowly wide of the post.
Antonio Valencia, such a cult figure during his time at Wigan, had to endure catcalls and jeers after going to ground in the 54th minute.
Yet the Ecuador winger was smiling two minutes later when he supplied the cross that led to the opening goal.
It came from Rooney - a fine header into the corner - and a landmark one as well. He savoured the moment and the goal was his reward for another typically hard shift.
That was the cue for United to turn the screw, and Berbatov added a second two minutes later. He started and finished the move cheekily chipping the ball over Kirkland before finding the net with his second touch after Scholes supplied the through ball.
United made it 3-0 in the 65th minute thanks to Rooney's second goal of the game. There was touch of luck about this effort as his shot took a slight deflection off Mario Melchiot to wrong-foot Kirkland after Berbatov had supplied the opening.
Rooney was given a rousing reception by the visiting fans when he was replaced by Owen in the 72nd minute.
It was damage limitation now for Wigan, who had lost at home to Wolves in midweek.
However, Owen made it 4-0 to United with his first goal for the club, a cool finish into the corner in the 85th minute after he had been set up by Nani.
And Nani had the final word himself with a superb free-kick in stoppage time from 25 yards that sailed over a stranded Kirkland's head.
