Scholes was joined in midfield by Ryan Giggs, who became the first player to reach 600 Premier League appearances, Michael Carrick and Nani.
Rio Ferdinand, celebrating his 400th games for the club, was part of a back four including Rafael, Vidic and new boy Alex Buttner, while Anders Lindegaard was handed another start ahead of David De Gea.
With Van Persie on the bench nursing a minor injury, Hernandez and Danny Welbeck were charged with shouldering the weight of the frontline.
The duo combined after five minutes, as the England striker was clipped by Al-Habsi and earned United a dubious penalty.
Welbeck’s fall was nothing short of dramatic and the visitors were left incensed by the decision.
Wigan’s sense of injustice did not last long as Hernandez planted the penalty to Al-Habsi’s left and saw his effort parried by the Wigan custodian.
Nani and Welbeck both went close to open the scoring, the former attempting a chip that drifted wide of the goal, the latter seeing his effort cleared off the line by Maynor Figueroa.
The second half resumes without changes and United were in front barely after the restart as Nani’s cross was parried into Scholes’ path who cooly converted home, scoring his 155th goal for the club.
The goal crucially swung the game United’s way.
Shortly after United had gone 1-0 up, Nani cut back across the goal, only for Welbeck’s overhead kick to drift just wide of the goal.
United finally had their second after 63 minutes as Buttner’s shot was turned past Al-Habsi by Hernandez, as the Mexican poached onto the debutant’s shot to make it 2-0 for the hosts.
Minutes later Buttner completed a remarkable debut as he brushed past Boyce before drilling a shot past Al-Habsi to notch his first goal for the club and put United 3-0 up.
Scholes and Giggs were withdrawn to make room for Powell and Van Persie with 19 minutes left, as the Dutchman looked to add to his remarkable tally of 52 goals in his last 58 Premier League appearances.
The former Arsenal man did indeed go close to his fifth goal in four games for United, but he failed to convert from the six-yard box as Al-Habsi gathered the ball.
United were to have a fourth goal, though, as Powell received the ball from Hernandez before jinxing past Caldwell and drilling the ball home for United’s fourth goal with just eight minutes to go .
Ferguson had called for defensive solidity ahead of the game and today’s performance would have pleased the Scot, particularly because Chelsea and City stumbled to away draws while the Reds picked up three points, but the first half was far from impressive and the performance will have to be addressed.
On a more positive note, Buttner looked the business on his debut, and without getting carried away, he could provide some much needed competition for Evra for the left-back spot. The attention now shift to Galatasaray's visit to Old Trafford on Wednseday, with United desperate to avoid the sort of stuttering start that cost them a place in Europe 12 months ago.