A Wayne Rooney penalty and a Nemanja Vidic header gave United a 2-0 halftime lead against a Wolves line-up showing 10 changes to the side that beat Tottenham Hotspur 1-0 on Saturday.
Antonio Valencia added a third goal in a pedestrian second half to put United joint top of the Premier League with 37 points, although Chelsea, who have a better goal difference, can restore their three-point lead against Portsmouth on Wednesday.
Aston Villa, who stunned United 1-0 at Old Trafford on Saturday, are third with 32 points after beating Sunderland 2-0 at the Stadium of Light.
Birmingham City are up to sixth after a 2-1 home win against Blackburn Rovers, their fifth league win in succession.
Bolton Wanderers moved out of the relegation zone, above Wolves, with a 3-1 home victory against fellow strugglers West Ham United who slipped to second from bottom.
Wolves fans taking their seats on a bitterly cold night at Old Trafford were scratching their heads when the team was announced with all 10 outfield players who started against Tottenham left out of the side by manager Mick McCarthy.
Premier League rules state that teams must play a full-strength side in every game, although a spokesman said it was unlikely that Wolves would suffer any punishment for a team selection that appeared designed to rest the first-choice side for Sunday's match against Burnley.
"We've just got a really busy period coming up," McCarthy told BBC Radio Five. "They were all first-team squad players who played tonight, not reserves and I have to say there were some really good performances.
"That team did as well as we did against Arsenal and Chelsea."
After holding United at bay for 20 minutes and even having a glorious chance volleyed over by George Friend, Wolves slipped away quietly once Rooney had tucked away his 12th league goal of the season following Ronald Zubar's needless handball.
Vidic effectively killed the game when his header evaded Wolves keeper Marcus Hahnemann shortly before the break while Valencia volleyed in after clever play from Dimitar Berbatov.
It was a good night for the city of Birmingham. Goals by England duo Emile Heskey and James Milner earned Villa their victory at Sunderland who had Lorik Cana sent off.
"It's been a great few days," manager Martin O'Neill told the BBC. "I was worried about this fixture but confidence is high and when confidence is high you can perform."
Cameron Jerome scored both Birmingham goals as they recorded their best sequence of results in the top flight since 1973.
