Elsewhere, Arsenal thrashed bottom of the table Southampton 6-1 to leave the newly promoted Saints still searching for their first points of the season.
At Old Trafford, Scholes got the ball rolling for United before two debutants in Alex Buttner and Nick Powell completed the scoring.
United missed the chance to take an early lead when Wigan's Ali Al Habsi saved Javier Hernandez's weak penalty.
It was a controversial spot-kick, won after Danny Welbeck dived in the box.
But after half-time Al Habsi could only weakly palm away Nani's cross, allowing Scholes to score his 163rd goal for United.
Hernandez then atoned for his spot-kick error by making it 2-0 after good work by veteran midfielder Ryan Giggs, playing his 600th Premier League game.
Dutch left-back Buttner, a recent signing from Vitesse Arnhem, then scored a superb solo goal, beating three men down the left before a shot from a tight angle went in off Al Habsi.
And eight minutes from time, midfielder Powell made it 4-0.
At the Britannia Stadium, England striker Peter Crouch gave Stoke a 15th minute lead when he bundled the ball in from close range.
But City, who've already had to come from behind to preserve their unbeaten start to the season, were level 10 minutes before half time when new signing Javi Garcia scored on his debut after heading in Carlos Tevez's free-kick.
Stoke defender Ryan Shawcross's goal-line clearance late on ensured a point for the Potters.
Arsenal struck in the 11th minute at the Emirates when Keiran Gibbs's cross was turned in to his own net by Southampton defender Jos Hooiveld.
Lukas Podolski then made it 2-0, just after the half hour mark, when he swung in a 25-yard free-kick over the wall.
Gervinho added Arsenal's third 10 minutes before half-time before another Gibbs-inspired own-goal, this time by Nathaniel Clyne, made it 4-0.
There was still time in the half for Saints to get on the scoresheet when Arsenal goalkeeper Wojciech Szczesny dropped a cross and Danny Fox smashed in the loose ball.
But Gervinho restored Arsenal's four-goal lead in the 71st minute when he tapped in from close range after substitute Aaron Ramsey's cross hit the post.
And, two minutes from time, Theo Walcott scored against his old club to make it 6-1.
At Loftus Road, there was no pre-match handshake from Anton Ferdinand for Chelsea captain John Terry.
The match was the first between the clubs since since Chelsea and England defender Terry was found not guilty of using a racial slur against the Hoops' Ferdinand in the corresponding fixture last October.
Terry is still the subject of a Football Association investigation over charges he has always denied.
The match ended goalless, with QPR duo Park Ji-Sung and Bobby Zamora both failing to make the most of good chances.
Aston Villa won their first league match under new manager Paul Lambert as they ended Swansea's unbeaten start to the season with a 2-0 home win.
Matthew Lowton gave Aston Villa a 16th-minute lead with a 20-yard volley before Christian Benteke's goal two minutes from time secured victory.
Former Manchester United striker Dimitar Berbatov scored twice as Fulham beat West Brom 3-0.
Berbatov, on his home debut, gave the Cottagers a 31st-minute lead when his well-struck shot from 15 yards beat Baggies goalkeeper Ben Foster.
West Brom's day got worse when they went down to 10 men after Nigerian winger Peter Odemwingie was shown a red card for lashing out at Fulham defender Sascha Riether.
Berbatov's penalty then made it 2-0 on the stroke of half time and Steve Sidwell completed the scoring a minute from time.
Norwich and West Ham shared the points in a goalless draw.
Sunderland are at home to Liverpool in Saturday's late kick-off, Reading face Tottenham on Sunday and Everton play Newcastle on Monday.