Peter Crouch became just the sixth player to score for six different Premier League clubs as he ended Manchester United's perfect start to the campaign in a 1-1 draw at the Britannia Stadium.
United, who had taken a first half lead through Nani, remain unbeaten and had the consolation of returning to the top of the Premier League, replacing neighbours Manchester City who had earlier beaten Everton 2-0.
But the defending champions are now only top on goal difference and, following a characteristically dogged display from Tony Pulis' side, could count themselves fortunate to have emerged with a solitary point.
United faced disruption for their testing visit to the Potteries even before kick-off when defender Jonny Evans was injured in the warm-up and substitute winger Antonio Valencia was forced into action at right-back.
However, despite the mounting odds, and the absence of Wayne Rooney who was rested for the occasion, the defending Premier League champions needed just 26 minutes to take a grip on the game.
Nani, who is enjoying an impressive start to the campaign, gathered the ball midway in the Stoke half and exchanged passes with Darren Fletcher and finished convincingly into the bottom right-hand corner from just inside the area.
United would have claimed they should have been in the lead earlier, after three minutes to be precise, when Phil Jones' punt forward was deflected off Crouch into the path of Javier Hernandez.
The Mexican streaked towards goal before falling to ground under a challenge from Jonathan Woodgate who could consider himself lucky not to have conceded a penalty.
Hernandez himself was less fortunate and injured himself in the incident, soon limping off to be replaced by Michael Owen.
That set the tone for a predictably full-blooded meeting as United aimed to continue their record of never having dropped a point to Stoke in the Premier League.
Before Nani's breakthrough, Rory Delap was forced to clear a Jones' set-piece header off his line before Crouch was in action at the other end of the field, heading disappointingly wide at the far-post from a Matthew Etherington corner.
David de Gea was coming through his test in the United goal impressively and saved superbly twice before the interval, first tipping Andy Wilkinson's determined shot onto the woodwork and then diving sharply to his right to turn away Jonathan Walters' low shot.
Opposite keeper Asmir Begovic was less sound in dealing with a Wilkinson back pass, under pressure from Ashley Young, and presenting Nani with an opening which the Portuguese international blazed into the stand.
But Stoke's resilience has never been in question and, even though Crouch is a new recruit to the Britannia, he certainly possesses that quality in abundance.
Crouch it was who, after 52 minutes, powered between Jones and Rio Ferdinand to meet Etherington's right-wing corner and head home his first goal since moving to the Potteries in the summer for a club record Â£10 million.
Goal number two almost followed two minutes later, courtesy of a fine cross from Jermaine Pennant. Crouch controlled the ball expertly on his chest but de Gea was again equal to the task, making a telling touch and blocking his attempt from no more than one yard.
As chances followed at both ends, United had another penalty appeal rejected, this one after an apparent trip by Woodgate on Dimitar Berbatov and Begovic parried a Young shot.
However, the momentum, and belief, was with Stoke and de Gea was again called into action, this time positioning himself well enough to beat out a fierce free-kick from Marc Wilson.