For the Latics, it was the same old boring story and their 10th defeat from 10 games against United since their arrival in the Premier League.
Rooney got the 100th goal of his career with a header to break the deadlock, Dimitar Berbatov got the second and Rooney enjoyed a slice of luck when his second deflected off Mario Melchiot to leave Chris Kirkland stranded.
Then Owen came off the bench to hit a trademark goal in off the right post after being set up by Nani, who added to Wigan's misery with number five in stoppage time.
New signing Mohamed Diame went straight into the Wigan side at the expense of Michael Brown - the only change from the side beaten by Wolves.
United made seven changes after the shock defeat at Burnley with Ben Foster, Patrice Evra, Wayne Rooney and Jonny Evans the only players retaining their places in the starting line-up.
It was goalless at half-time but United were kicking themselves after creating chances but again showing a lack of finishing power.
They could have had it sewn up in the opening 10 minutes but Titus Bramble came up with a super block to deny Darren Fletcher and then Paul Scholes blazed over from close range.
Kirkland had no problem dealing with goalbound efforts from Rooney and Berbatov before the Latics came up with their first real threat.
Jason Koumas cut inside to let fly with a powerful right footer which looked destined for the left corner but Foster did well to get both hands to it to keep it out.
Earlier Wigan had a half-hearted penalty appeal waved away by Howard Webb after Jordi Gomez went down under a challenge from Nemanja Vidic.
Paul Scharner went close for the Latics in the second half by heading over after Patrice Evra was penalised for a cynical foul on Charles N'Zogbia.
And seconds after Rooney's opener - with Wigan old-boy Antonio Valencia supplying the cross - Wigan went desperately close when Hugo Rodallego's header forced Foster to show his agility with a great save.
But United hit back instantly with Berbatov getting number two after lifting the ball over Kirkland, before Rooney left the Latics with no way back and Owen's strike saw Wigan fans heading for the exits.
Nani made it five from a free-kick in the closing seconds to complete the rout.