Well, it had to happen eventually.
Still, the 1-1 draw was enough to see them go back to the top of the table, and they have a few days to take stock, reload, and hope nobody else goes down to an injury before the game at FC Basel in the Champion's League.
Here are five thoughts from what turned out to be an eventful game.
The Red Devils officially have an injury crisis. Now, more than ever, United's squad depth will be tested.
Before the game even started, two important players had to drop out of the reckoning. Their absences had a knock-on effect on how the game proceeded and led to an unusual selection at the back.
With Chris Smalling already out due to an injury, Phil Jones was set for a start at right-back. But Jonny Evans, who would have lined up alongside Rio Ferdinand, picked up an injury in training, which necessitated a move back to the center for Jones. This led Sir Alex to select winger Antonio Valencia to take the fullback slot.
The other pre-match injury was none other than star player Wayne Rooney. His absence in particular was keenly felt. After Stoke scored the equalizer, United fans were left waiting for somebody, anybody, to grab the game by the scuff of its neck take control. Usually, that man would be Wayne Rooney, capable of winning a match through sheer force of will.
Sadly, nobody "pulled a Rooney" and United were left wanting at the end.
In addition to the pre-match knocks, both Javier Hernandez and Patrice Evra picked up injuries over the course of the game. It remains to be seen how much time, if any, they will miss.
Rafael, Smalling, Evans, Nemanja Vidic, Darron Gibson, Tom Cleverley, Rooney, Hernandez, Evra... if the season continues this way, we may just end up seeing Premier League debuts for the likes of Paul Pogba and Ravel Morrison.
Stoke had a plan for how to deal with the young Spanish keeper: stick Peter Crouch down his throat on set pieces and Rory Delap throw-ins and watch the goals rack up.
The plan worked to some extent, as it was off a set piece that Crouch lost his marker (Phil Jones), barreled down the six-yard box, and headed in a cross that De Gea should have dealt with. On other occasions, the United Defence held strong, but it remains clear that De Gea needs to work on dealing with the physical play of the Premier League.
But despite showing that weakness in his game, he also showed something else: Edwin van der Sar reincarnated.
Like the retired Dutch master, De Gea is a supremely gifted shot-stopper and he showed excellent reflexes in making several key saves. And like the Dutchman, the Spaniard has a knack for quickly turning defence into attack through an above average distribution. Hardly any of De Gea's kicks, throws, and clearances went astray, and it's easy to see him finishing the season as the goalkeeper with the most assists in the league.
Here's another telling stat as well: as of the end of the game, De Gea has the most saves in the Premier League.
The opening goal of the contest was a well worked one, almost Barcelona-like in execution. The move, filled with flicks and one-twos between Darren Fletcher and Nani, ended with the Portuguese international coolly dribbling past a defender and slotting the ball home.
It was the second weekend in a row where Nani showed his class as a goal scorer, and has prompted many to think that maybe, just maybe, he might be stepping out of Ronaldo's considerable shadow.
He has the flair, the skill, and the shot that Ronaldo has, but Nani also has a better sense of teamwork. When Ronaldo was on United, his ego grew and grew as the years went on, so much so that it began to look like he considered everyone else a supporting act.
Nani, on the other hand, is a much better team player and you see it in his attitude, the fact that he is never as petulant as Ronaldo, and the fact that he doesn't dive nearly as much.
This season, we've seen Anderson primarily paired with Tom Cleverley, Darren Fletcher and Michael Carrick in the center of the park. Each of these men bring something different to the table, but only one of them really compliments the Brazilian's game.
Michael Carrick brings pinpoint passing ability, but he is slow and lacks the attacking confidence to really boss a game.
Darren Fletcher brings the steel and grit; the never-say-die attitude that Roy Keane used to bring to the side. But, although he has some passing ability, he lacks pace and technical flair.
When Anderson plays alongside either of these two, he ends up having to do much more than he's used to, and it leads to a drop in effectiveness. Already, we've seen an alarming number of long passes intercepted. And, more often than not, Anderson has been stuck in the United half of the field having to make up for Carrick or Fletcher's lack of pace.
Cleverley is a midfielder of a different sort. A classic box-to-box player in the Cesc Fabregas mold, he's neither the best passer of the ball nor the steely ball winner that Carrick or Fletcher are, respectively.
Rather, he is much like Anderson. Both are high energy players who love to run up and down the pitch, putting in the tackles when necessary, and they both have skill in bringing the ball into attack. Most importantly, they both have enough pace and energy to cover for each other, a trait that allows Anderson more freedom to play his game.
Neither Anderson nor Cleverley is the best midfielder in the world, but as a unit, they are probably each other's best partner.
With Wayne Rooney out of the side, Sir Alex Ferguson gave Dimitar Berbatov a rare premier league start, charging the Bulgarian with leading the attack.
Sadly, Berbatov showed a lot of the facets of his game that have led United supporters to lose faith in him. He was sluggish throughout, petulant and lackadaisical, careless with the pass, and never looked to be a serious threat to Stoke's defense. He showed some flashes of his old golden-boot self, but it wasn't enough and he was taken off for Danny Welbeck late in the game.
You could say that he was ineffective due to a lack of playing time, but even Michael Owen, who has had even less playing time, outplayed the Bulgarian. And when Welbeck came on, the United attack looked a lot more dangerous.
All of this means that Berbatov's time at Old Trafford looks to be numbered, and he needs to step it up if he wants playing time once everyone is healthy.
So there you have it: United dropped their first points of the season in a game that could actually have gone much worse if not for the heroics of David De Gea.
What were your thoughts about the game?