The decision came within hours of a shock 2-1 defeat in the FA Cup third round by Coventry City, three leagues below them.
"We would like to thank Mark for all he has achieved for the Club over the last four and a half years, notably in guiding us to three successive ninth-place finishes in the Premier League, and we wish him every success for the future," Stoke said in a statement.
"The Club will look to appoint a new manager as soon as possible and will be making no further comment at this time."
Keeping Stoke in the top half of the table for three successive campaigns was followed by a drop to 13th last season and an unsuccessful transfer window with new signings having made little impression.
This season they have fallen into the Premier League relegation places and have lost six of their last eight games in all competitions, having won only five league matches out of 22.
Hughes did not help himself by fielding a weakened team in a 5-0 defeat at Chelsea last weekend to save players for what he felt was a more winnable game at home to lowly Newcastle.
They lost 1-0, dropping into the bottom three, before the FA Cup humiliation at Coventry in his 200th game at the club.
"We've got good owners who will make the right decisions for the club," Hughes said before learning that the previously supportive board had decided they needed a change.
Stoke do not play again until travelling to Manchester United on Monday week in the Premier League but they will hope to appoint a successor quickly enough to strengthen the squad before the transfer window closes at the end of the month.
The 54-year-old Hughes has a wealth of managerial experience at Blackburn Rovers, Manchester City, Fulham, Queens Park Rangers and Stoke as well as five years in charge of Wales - who currently have a vacancy after the departure of Chris Coleman to Sunderland.
(Reporting by Steve Tongue,; Editing by Ed Osmond)
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