The hosts, who dropped into the bottom three due to results in the day's early games, took the lead in the first half when Charlie Adam's long-range free kick deflected off Michael Carrick and past David de Gea.
Robin van Persie equalised for the visitors right after the restart, but they were level for just five minutes as Adam secured the victory with a stunning strike into the top corner from the edge of the box.
Here, Sports Mole takes an in-depth look at a historic afternoon for Stoke at the Britannia Stadium.
On target: 6
On target: 4
Was the result fair?
Looking at the stats, you'd have to say no, but it is hard to begrudge Stoke their victory this afternoon. They defended heroically and the possession stats will have been largely affected by the final 10 minutes or so, when Stoke simply invited pressure onto themselves and held firm against the constant United attacks. Over the entire 90 minutes, things were pretty even between the sides, but there is little doubt that United's plans were hit by injuries to their two starting centre-backs in the first half. A draw probably would have been the fairest result, but manager Mark Hughes will certainly be arguing that his side deserved their victory.
When you're in a relegation dogfight, perhaps the most important attribute to be able to call upon is heart. Stoke showed plenty of that this afternoon as they hurled their bodies in the way of anything United threw at them. There was some heroic defending going on towards the end and not even the new trio of Juan Mata, Robin van Persie and Wayne Rooney could pick a way through their stubborn defence. As is often the case with Stoke, it wasn't the prettiest of victories - with the exception of Adam's winning goal - but it was effective, and that is far more important for them at the moment. They had their fair share of luck throughout the match, but it was mostly sheer hard work that earned them the three points this afternoon. Hughes will be delighted with his side, and rightly so.
Man United's performance
All the pre-match talk centred around the Mata-Van Persie-Rooney partnership linking up for the first time, but the reality of the trio was underwhelming. They struggled to combine effectively against Stoke's tough defence, only really managing to do so once when Mata fed Van Persie for United's only goal. There is no doubt that the injuries to Jonny Evans and Phil Jones had an impact on the team as Michael Carrick had to drop back into defence and Rooney filled in midfield, but that was a conscious decision from manager David Moyes as he had the alternative of Darren Fletcher on the bench, which would have enabled him to keep Rooney up front. All in all, the tempo was too slow for United today, and that allowed Stoke to gather themselves and create a formidable defensive wall. The Red Devils had their chances to equalise, most notably when Tom Cleverley blazed over after Rooney had hit the post, but they certainly didn't do enough to win the game today. Another disappointing afternoon for Moyes and United.
Sports Mole's man of the match
Charlie Adam: Charlie Adam will not have had many better performances than today's in a Stoke shirt. He was full of energy from start to finish and seemed to thrive in the tough conditions. Whether he has one or two goals to his name remains to be seen after his first took a big deflection off Carrick, but he deserves the 'man of the match' award for his second strike alone. He gave De Gea no chance with a rocket into the top corner that proved to be the winner. The Scot received a fair amount of stick from the away fans due to his past ties to Liverpool, but he can feel happy that he answered them on the pitch with a fine display this afternoon.
This one has to go to Michael Carrick for his part in the opening goal. Some would see it as bad luck, whether it turns out to be an own goal or a Charlie Adam strike, but Carrick certainly should have done better. He simply left a hanging wayward leg out to block the powerful effort, and that was never going to be enough. Of course, he had no way of knowing that his lacklustre block would result in diverting the ball past his own keeper, but the risk was high enough to know that a more assertive piece of defending was needed.
Neil Swarbrick had a good game today, keeping control of a match that threatened to get a little feisty at times. It was certainly a physical encounter, as it usually is with Stoke, but the referee did not make any rash decisions and got most of his calls right.
Stoke: Next up for Stoke is a tricky trip to St Mary's Stadium where they will face Southampton next Saturday.
Man United: United, meanwhile, will look to get their Champions League challenge back on track when they host Fulham at Old Trafford next Sunday.