Robin van Persie ended his goal drought as Manchester United restored their 15-point lead at the top of the Premier League table and deepened Stoke's relegation worries.
Van Persie had gone 10 domestic matches without scoring but won and then converted a penalty in the 66th minute to make the points safe.
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Michael Carrick had opened the scoring inside four minutes and United now need only seven points from their remaining six games to ensure they cannot be caught by Manchester City.
Stoke dropped to 16th before kick-off after Sunderland's win over Newcastle and, having taken only one point from their last seven games, are looking below them with ever increasing concern.
Captain Nemanja Vidic was back from a calf injury in one of four United changes from Monday's derby defeat while Stoke boss Tony Pulis had Glenn Whelan fit but Matthew Etherington and Marc Wilson were out so Charlie Adam and Andy Wilkinson started.
Last season Stoke picked up their first Premier League point against United and went unbeaten against the big six at the Britannia Stadium.
Their home fortress has been anything but in recent weeks, though, with West Ham and Aston Villa both taking away maximum points, and what the Potters really could not afford was a bad start.
But they made exactly that, conceding a fourth-minute corner that they failed to clear, allowing Carrick to prod beyond the despairing dive of Asmir Begovic.
With Wayne Rooney dictating play from a deep-lying midfield role, United were completely in control.
Rooney was given space and time to take aim from 25 yards with a shot pushed away by Begovic as Stoke struggled even to touch the ball.
Discontent among the Stoke fans has been growing but they were fully behind their team and had cause for optimism in the 19th minute when Adam won a free-kick wide on the right and Whelan's cross was headed just wide by Robert Huth.
The difference in confidence was all too clear, though, with United zipping the ball around while Stoke touches were heavy and passes misplaced.
Begovic was forced into another save just past the half-hour mark, scooping a Van Persie shot from a narrow angle behind.
Stoke at least finished the half well as Wilkinson - sporting a bandage on his head after being caught by a high Javier Hernandez boot - barrelled down the right and into the area before seeing his shot blocked by Vidic.
Stoke had the strong wind behind them in the second half but it was United who began the brighter and Van Persie had the chance to end his drought when he was played in by Hernandez but shot into the side-netting.
At the other end, Jon Walters had a decent opening when Ryan Shotton headed a deep cross into the centre but the striker could not keep his shot down.
An encouraging sign for Stoke was the increasing influence of Adam, and the midfielder tested David de Gea for the first time in the 59th minute with a well-struck shot from long range.
But the Potters' hopes were dealt a crushing blow when they gave away a penalty. A flowing move that began with Phil Jones holding off Walters in United's right-back spot progressed through Antonio Valencia and Rooney, who picked out Van Persie in the area.
The Dutchman cut inside Wilkinson, who tripped him, and Van Persie stepped up to tuck his spot-kick smartly into the bottom corner before running to the touchline to celebrate with Sir Alex Ferguson.Stoke's hopes of taking anything from the game were all but over but they kept pressing and Ryan Shotton forced a decent save from De Gea, who then reacted very well to push Adam's clever free-kick behind when it was heading for the bottom corner.
Pulis threw on Cameron Jerome, former United man Michael Owen and Peter Crouch but there was little threat and Stoke remain only three points clear of 18th-placed Wigan, who have two games in hand.