Paul Scholes scored the only goal after 73 minutes at Molineux as United overcame the loss of 28-goal Wayne Rooney, who was sidelined with a knee injury, and moved two points ahead of Chelsea, which plays in the FA Cup on Sunday, and Arsenal, which beat next-to-last Burnley 3-1. Chelsea has a game in hand on both.
The Wolves defence failed to clear a cross from Nani and Scholes moved the ball into space inside a crowded area and beat goalkeeper Marcus Hahnemann with an angled shot for his 100th Premier League goal.
Wolves striker Sam Vokes squandered a golden chance to equalise in stoppage time when he was found unmarked in front of goal but lifted the ball over the bar from six metres.
Arsenal captain Cesc Fabregas fired home Samir Nasri's cross in the 34th minute for his 17th league and cup goal of the season but he went off with what appeared to be a right hamstring injury before halftime.
"How big the damage is we don't know yet because it's too early," said Arsenal manager Arsene Wenger, whose team faces FC Porto in the Champions League on Tuesday and has to overturn a 2-1 deficit. "We'll see tomorrow and Monday. We will have to make a late decision if he plays on Tuesday certainly."
David Nugent equalised from Leon Cort's pass but Theo Walcott regained Arsenal's lead in the 60th minute for his first goal in 18 appearances, and Andrey Arshavin added the third in injury time.
Manchester United has 63 points from 29 games, Chelsea has 61 from 28 and Arsenal 61 from 29.
In the other Premier League game, Bolton won 2-1 at West Ham to improve its chances of avoiding relegation and push the home side deeper into trouble.
Kevin Davies headed the first from close range and provided the cross for Jack Wilshere to score his first goal for Bolton since his loan move from Arsenal. Alessandro Diamanti's reply for West Ham came only two minutes from the end. The victory moved Bolton up to 13th and five points above the relegation zone while West Ham is only three points away from danger.
On Sunday, Everton welcomes Hull and Liverpool goes to Wigan on Monday.
In FA Cup action, Frederic Piquionne scored twice in four minutes to give Portsmouth victory over Birmingham as the club reached the last four two years after winning football's oldest domestic cup competition.
But the visitors were unhappy that referee Steve Bennett ruled out a goal which TV replays showed crossed the line. By coincidence, it happened on the day that the International Football Association Board ruled out any more experiments with goal-line technology to decide such incidents.
Portsmouth, which is in financial administration and last in the Premier League standings, was 2-0 ahead when Liam Ridgewell's 81st-minute close-range header for Birmingham crossed the line before goalkeeper David James blocked it. But Bennett ruled it was not a goal.
"We should have had a lifeline with a perfectly legitimate goal but unfortunately it wasn't to be," said Birmingham manager Alex McLeish. "It would have given us a lifeline and I wouldn't bet against my team coming back if we got that goal.
"You would expect an official at this level to see that. They do the fitness tests and part of that is the vision side of things. It's a shame the guy missed that, I'm sure he will be hurting about it."
Asked if Birmingham scored a goal, James said: "Not as far as I was aware."
"Maybe we can debate that all the way home," James said. "We won 2-0 as far as the score goes and I think we deserved it."
Fulham and Tottenham fought out a 0-0 draw at Craven Cottage in a quarterfinal of few clear-cut chances. Tottenham defender Vedran Corluka almost turned a cross into his own net with a minute to go.
On Sunday, defending champion Chelsea hosts Stoke and Aston Villa goes to Reading, the League Championship club which knocked out Liverpool in round three.
Newcastle crushed Barnsley 6-1 and opened up an eight-point advantage at the top of the League Championship in its bid to go straight back to the Premier League after last season's relegation.
Nottingham Forest beat Swansea 1-0 to regain second place from West Bromwich Albion which lost 3-1 at Queens Park Rangers.
