With second placed Arsenal preparing for Sunday's League Cup final against Birmingham, Sir Alex Ferguson's side were able to cement first place thanks to goals from Hernandez, Rooney and Fabio Da Silva at the DW Stadium.
Ferguson opted to leave Dimitar Berbatov on the bench as Hernandez started up front alongside Rooney and the Mexican striker repaid his manager's faith with the opening goal in the 17th minute.
Nani raided down the left wing and curled over a cross that Hernandez poked in at the near-post for his 12th goal of the season.
Rooney had earlier angered Wigan when he caught James McCarthy with an elbow to the back of the midfielder's head, but referee Mark Clattenburg decided not to punish the United forward.
United were indebted to goalkeeper Edwin van der Sar for several crucial saves before Hernandez killed off second bottom Wigan with a typically predatory strike in the 74th minute.
Rooney's 84th minute goal and Fabio's strike three minutes later ensured United head into this week's crucial fixtures at Chelsea and Liverpool on a high.
Aston Villa eased their relegation worries by thrashing Blackburn 4-1 at Villa Park.
Gerard Houllier's side went in front when Keith Andrews conceded possession to Ashley Young in the area and then hauled down the winger, who picked himself up to score the resulting penalty in the 49th minute.
An own goal from Blackburn youngster Grant Hanley in the 62nd minute put Villa in control and Stewart Downing sealed the win two minutes later as the hosts moved five points above the bottom three.
Nikola Kalinic got one back for Rovers in the 81st minute with a deflected effort, but it was little consolation for Steve Kean's team as Young struck again one minute later.
Blackburn's dismal day was complete when New Zealand defender Ryan Nelsen was sent off in the closing stages for a second booking.
Wolves climbed out of the relegation zone with a 4-0 demoliton of 10-man Blackpool at Molineux.
Mick McCarthy's side made a dream start as Adam Hammill's surging run in the second minute ended with a pass to Matt Jarvis and the winger drove his shot past Richard Kingson.
Blackpool's task was made even harder just before half-time when DJ Campbell was sent off for pushing Richard Stearman in the face.
Wolves took full advantage of their numerical superiority thanks to Jamie O'Hara's cool finish in the 54th minute before two late goals from Sylvan Ebanks-Blake sealed Wolves' biggest Premier League win.
Everton striker Jermaine Beckford scored twice to seal a 2-0 win against Sunderland at Goodison Park.
David Moyes' side took the lead in the eighth minute when Beckford pounced on Leon Osman's pass and fired in a shot that deflected into the net off Sunderland defender Titus Bramble.
Beckford has endured a difficult time since his pre-season move from Leeds but he bagged his second in the 39th minute with a scuffed finish from Mikel Arteta's cross as the Toffees leapt up to 10th place.
Newcastle held on for a 1-1 draw against Bolton at St James' Park despite the second half dismissal of Ryan Taylor.
Kevin Nolan netted against his former club in the 13th minute when the Newcastle captain headed in Cheik Tiote's cross.
But Bolton forward Daniel Sturridge equalised in the 38th minute, lashing in his fourth goal in four games since his loan move from Chelsea.
Newcastle were reduced to 10 men just after half-time when Taylor, who was only playing due to Joey Barton's injury in the warm-up, saw red for a two-footed lunge on Johan Elmander.