Gary Rowett's Potters were beaten 3-0 at home by Wigan Athletic and saw Ashley Williams dismissed, leaving them second from bottom, with the Owls moving up the table after ending Millwall's unbeaten start to the campaign.
Aston Villa and Brentford missed the chance to send a message to other Championship promotion- hopefuls by playing out an entertaining 2-2 draw in front of Everton winger Yannick Bolasie, reportedly set to join Steve Bruce's side on loan.
And a pair of Charlie Mulgrew penalties saw Blackburn Rovers come from two goals down at home to deny Reading its first win of the league season.
After appointing former Derby County boss Rowett, Stoke was among the pre-season favourites for promotion, having retained stars including England goalkeeper Jack Butland and Wales midfielder Joe Allen following relegation.
But things are not going to plan and after four matches Stoke have collected just two points, with Wigan good value for its 3-0 win at the bet365 Stadium on Thursday (AEST).
Gavin Massey set up Will Grigg for their 27th-minute opener and quickly added the second himself to lay the foundations for a comfortable victory for Paul Cook's men, who had not won since opening day.
When Allen brought down Nick Powell in the box, Grigg added his second goal of the game from the penalty spot, with Stoke's misery complete when Williams saw red for a second bookable offence 12 minutes from time.
Bolasie is expected to add to Wednesday's capture of Anwar El Ghazi on a season-long loan from Lille and Aston Villa showed it could use the duo's wing wizardry as it needed a last-gasp leveller to earn a point against top-six rival Brentford.
Neal Maupay hit a brace to take his tally to five Championship goals this season, a fine volley in the first half added to by an instinctive poacher's finish in the 82nd minute.
Jonathan Kodjia had already equalised once with a superb solo strike and the Villa striker came up with a headed leveller in the fifth minute of added time to ensure the spoils were shared at Villa Park.
Few tipped Bolton to be among the second tier's big boys this term, but Phil Parkinson's men sit third - ahead of Villa and Brentford - after Will Buckley earned a 1-0 home win over Birmingham City, although Josh Magennis also claimed the decisive goal.
A Barry Bannan screamer put Sheffield Wednesday on track for its first win of the campaign, with Tom Lees doubling its lead at home to Millwall, and although Ryan Tunnicliffe responded for the visitor the Owls held firm.
Reading also looked to be collecting its first triumph of the league campaign, going 2-0 up at Ewood Park thanks to a first-half brace from Jon Dadi Bodvarsson.
But Rovers captain Mulgrew converted twice from 12 yards, both penalties conceded by Paul McShane, to make sure Paul Clement's wait for a Royals win goes on.
Whether Preston North End was affected by Carrow Road's pink dressing room remains to be seen, but Norwich City beat it 2-0 thanks to late goals from Teemu Pukki and Alexander Tettey.