After a low-key first half Wayne Rooney scored twice to reach 100 goals for United while summer signing Michael Owen opened his account for the club late on and Nani completed the rout.
Abou Diaby helped free-scoring Arsenal to the top of the embryonic table, scoring twice in a 4-1 home defeat of struggling Portsmouth to take the Gunners' goal tally to 10 in their opening two matches.
Manchester City joined Arsenal and United on six points with 1-0 home win against Wolverhampton Wanderers while Sunderland also earned their second win of the season, coming back from a goal behind to beat Blackburn Rovers 2-1.
Hull City beat Bolton Wanderers 1-0 while Birmingham City and Stoke City ended 0-0 -- the first draw of the new Premier League season.
United finally clicked into gear after a stuttering start to the season, although it took a while for their superiority to convert into goals at Wigan who gave a debut to French midfielder Mohamed Diame, signed late on Friday.
Former Wigan winger Antonio Valencia, the man handed the task of trying to fill the gap left by Cristiano Ronaldo's transfer to Real Madrid, unlocked the defence of his old club after 56 minutes.
With time and space to cross, he picked out England striker Rooney who made no mistake with a header to notch a century of goals for the club he joined from Everton in 2004.
United keeper Ben Foster made a great save to deny Hugo Rodallega a minute later and in a frantic spell the visitors, going for a fourth consecutive title, then doubled their lead through Dimitar Berbatov.
Rooney's second, a deflected shot, killed off Wigan before Owen, who missed chances in both United's opening games, finally struck with a shot off the post. Nani made it 5-0 in stoppage time.
Arsenal were equally impressive as they maintained a storming start to the season which included a 2-0 Champions League playoff, first leg win at Celtic in the week.
With the Emirates crowd being treated to regular updates from the Ashes test at the Oval, the home side looked set to post a cricket score as they sliced through Portsmouth at will in a scintillating start.
Midfielder Diaby opened the scoring after 18 minutes after clever play from Eduardo down the left and he doubled the lead three minutes later when played in by Emmanuel Eboue.
Portsmouth pulled a goal back before halftime through Younes Kaboul and were unlucky after the break when John Utaka appeared to be tripped after outpacing William Gallas and surged towards Manuel Almunia's goal.
Gallas escaped any punishment and minutes later he popped up at the other end to make it 3-1, stabbing in from close range. Aaron Ramsey, a halftime substitute for Cesc Fabregas, capped a satisfying afternoon for the Gunners with a well-taken fourth.
Portsmouth, beset by financial worries, have now lost their opening three games and they suffered another blow when goalkeeper David James limped off late on.
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