After a poor start one win in the opening five matches Michael O'Neill was sacked by the board and replaced by Sunderland manager Alex Neil.

High scoring victories over Blackburn Rovers, Coventry, Huddersfield Town, Reading, Sunderland and Swansea City pulled Stoke clear of trouble and into mid-table.

In February 2022 Stoke announced a five-year multi-million pound refurbishment programme for the bet365 Stadium and the Clayton Wood Training Ground beginning in the summer of 2022 with the replacement of 8,400 seats in the Franklyn Stand and regeneration of The Players' Lounge and Delilah’s Bar.

[4][5][6] Leaving the club in the transfer window were Benik Afobe, Joe Allen, James Chester, Alfie Doughty, Steven Fletcher, Tom Ince, Christian Norton, Tashan Oakley-Boothe, Tommy Smith and Mario Vrančić.

Whilst coming into the team were Harry Clarke, Aden Flint, Dwight Gayle, Gavin Kilkenny, Josh Laurent, Liam McCarron and Will Smallbone.

[17] City were second-best against Middlesbrough and looked to be heading for a 2–1 defeat before a late header from D'Margio Wright-Phillips earned Stoke a fortunate 2–2 draw.

[21] Dean Holden took caretaker charge of the match against Blackburn Rovers as a long range goal from Baker earned Stoke their first away win of the season.

[40] Stoke put in a poor performance against West Brom, losing 2–0 before the season took a four week break due to the 2022 FIFA World Cup.

[49] Loanees Harry Clarke and Tariqe Fosu both returned to their parent clubs before Stoke ended a run of three successive defeats with an emphatic 4–0 win over Reading.

[50] Neil added more loan players to his squad, goalkeeper Matija Sarkic, defenders Ki-Jana Hoever and Axel Tuanzebe, midfielders Bersant Celina and Ben Pearson whilst Harry Souttar completed a £15 million move to Leicester City.

[51] New signings Celina and Sarkic made their first league start away at in-form Luton Town as Pelly Ruddock Mpanzu scored the only goal of the game,[52] this was followed by a drab goalless draw against Hull City.

[53] Stoke then took on bottom of the table Huddersfield Town, winning 3–0 with goals from Jagielka, Brown and late penalty from Baker whilst the Terriers had Will Boyle sent-off for two bookable offences.

[61] Stoke ended March with a frustrating goalless draw against Norwich City after they were denied by an inspired performance from former loanee goalkeeper Angus Gunn.

[66][67] City drew 1–1 at Cardiff with Jack Bonham saving a penalty from Sory Kaba and lost a 11th home match of the campaign against Queens Park Rangers.