First half goals from Matthew Upson and Peter Crouch saw the Swans beaten 2-0 at the Britannia Stadium.
Upson headed home from Matthew Etherington's corner after 25 minutes before Crouch's header from a Ryan Shotton long throw crept over the line.
It could have been a different story, with the Swans seeing a major chance to open the scoring after two minutes but Scott Sinclair saw his effort from ten yards fly over the goal.
Late on, Steven Caulker saw his header tipped on the crossbar after a superb reflex save from Asmir Begovic, but the Swans couldn't find their way through a resolute defence.
The big news from the Britannia was the absence of Michel Vorm, with the Dutch keeper missing out with a virus.
That meant Gerhard Tremmel made his first Premier League appearance since his move to the Liberty last summer.
Joe Allen was the other change from the side that lost to Norwich, with Josh McEachran dropping to the bench.
Stoke: Asmir Begovic, Andy Wilkinson, Ryan Shawcross (capt), Matthew Upson, Marc Wilson, Ryan Shotton (Wilson Palacios, 88), Glenn Whelan, Dean Whitehead, Matthew Etherington (Cameron Jerome, 68), Jonathan Walters, Peter Crouch (Rory Delap, 88).
Subs: Thomas Sorensen, Kenwyne Jones, Ricardo Fuller, Jermaine Pennant.
Swans: Gerhard Tremmel, Angel Rangel, Steven Caulker, Ashley Williams (capt), Neil Taylor, Leon Britton, Joe Allen, Gylfi Sigurdsson, Nathan Dyer (Luke Moore, 71), Scott Sinclair (Josh McEachran, 71), Danny Graham.
Subs:Alan Tate, Garry Monk, Mark Gower, Wayne Routledge, Leroy Lita.
Referee: Howard Webb
The Swans carved open an amazing chance within the opening two minutes as Angel Rangel sent a through ball for Nathan Dyer to run onto. The winger found Scott Sinclair ten yards out right in front of goal, but he blasted his effort way over the crossbar.
It was the visitors who were dominating possession and dictating play, with Sinclair and Nathan Dyer working themselves into decent positions but not getting the shot away.
The home crowd were starting to get frustrated, but after 25 minutes they were cheering as Stoke got themselves in front. Matthew Etherington swung a curling corner into the box and Matthew Upson rose to powerfully head home, giving Gerhard Tremmel no chance.
Gylfi Sigurdsson went close to equalising as his free-kick dropped onto the top netting before Neil Taylor embarked on a superb run before seeing his shot blocked by Upson for a corner.
But the home side struck again after 39 minutes, Ryan Shotton's long throw being met by Peter Crouch, whose header couldn't be kept out despite Tremmel's attempts.
Half-time: Stoke 2 Swans 0
The Swans went looking for an early goal to get themselves back into the game, and Dyer went close as his curling left-footed effort bounced just wide of the far post.
Stoke replied, another long Shotton throw was flicked on by Crouch and Jonathan Walters headed over from eight yards.
The Swans worked a decent chance for Angel Rangel after neat work by Dyer, but the Spaniard saw his effort deflected wide for a corner.
Brendan made a double change for the last 20 minutes, Luke Moore and Josh McEachran replacing Dyer and Sinclair.
Moore's neat twist and shot on the turn flew straight at Asmir Begovic before Sigurdsson's poked shot bundled wide.
Steven Caulker saw his header fantastically tipped onto the crossbar by Begovic in added on time, but the Swans couldn/t find a late consolation.