Michael Carrick toe-poked United ahead with a scrappy goal after four minutes and Robin van Persie ended his 10-match scoring drought with a 66th-minute penalty to seal the points in a game United dominated from start to finish.
They now have 80 points from 32 games, 15 clear of current champions Manchester City, who have 65 with seven matches to play.
City were not in league action at the weekend as they were facing Chelsea at Wembley in an FA Cup semi-final on Sunday.
"It was an important win and we are one game closer to the title. The important thing is not to take our eye off the ball," United manager Sir Alex Ferguson told Sky Sports.
At the other end, Sunderland won their first match under new manager Paolo Di Canio, beating Newcastle United 3-0 in a thunderous Tyne-Wear derby to boost their survival chances.
It was their biggest win over their arch-rivals at St James' Park since 1966 and their first there since 2000.
The win, their first for 10 league matches, came thanks to goals from Stephane Sessegnon, Adam Johnson and David Vaughan, and together with Stoke's defeat, lifted Sunderland into 15th place with 34 points.
Stoke, who have now taken just one point from a possible 21, slipped back to 16th with 34 points, level with Sunderland and Aston Villa and just three clear of FA Cup finalists Wigan Athletic in 18th.
DOMINANT UNITED
United, who stumbled when they were beaten 2-1 at home by Manchester City on Monday, had it easy against a Stoke side, who never looked like getting anything from the game after falling behind in the fourth minute.
The hosts' defence failed to clear a United corner and the ball bobbled around in front of goal before Carrick reacted to poke it past Stoke goalkeeper Asmir Begovic.
Wayne Rooney was playing deeper than usual in midfield and with Nemanja Vidic restored to the United defence alongside Rio Ferdinand, they looked composed at the back.
On the odd occasion when Stoke did threaten, improving United goalkeeper David de Gea dealt with everything.
United sealed the points when Van Persie, who had not scored for his side for just over two months, slammed in his penalty after he had been fouled by Andy Wilkinson.
"It was a big win. It was important that we bounced back from last Monday," said Van Persie, after netting his 20th league goal of the season.
"My goal came at an important time, but I wouldn't have cared who scored the goal. Every single player battled out there and we deserved it."
PASSIONATE CELEBRATION
Sunderland also ran out convincing winners in the earlier game of the day which turned out to be a one-sided derby which left Newcastle on the fringe of the relegation battle with 36 points from their 33 games.
Di Canio, who replaced Martin O'Neill and saw them beaten in his first match in charge at Chelsea last week, celebrate
