bottom club Sheffield Wednesday.
The 42-year-old Scot spent 16 months in charge in the Potteries after leaving fellow Championship side Sunderland to join Stoke in August 2022.
He led Stoke to 16th last season, a fall from the previous two campaigns, when they had each time finished 14th.
But they have struggled this term and currently sit 20th in the table.
Despite an expensive 18-man summer overhaul, the Potters have won just six of their 20 league matches.
Assistant Martin Canning has also left the club and Paul Gallagher will take charge of the team for Tuesday's home game against Swansea.