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Hughes was already on the brink of being dismissed prior to the 2-1 loss at fourth-tier Coventry following a miserable run that left the team languishing in the Premier League relegation zone.
The limp nature of Stoke’s FA Cup exit proved the final straw as Hughes was axed three hours after the final whistle at the Ricoh Arena.
“Stoke City can confirm that the contract of manager Mark Hughes has been terminated with immediate effect,” a statement on the club’s Twitter account read.
“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 places finishes in the Premier League, and we wish him every success for the future.
“The club will look to appoint a new manager as soon as possible and will be making no further comment at this time.”
Hughes’ 200th game in charge of Stoke proved to be his last after Jack Grimmer’s second half strike gave Coventry the biggest upset of the third round so far.
Charlie Adam had equalised with a 54th-minute penalty after Jordan Willis opened the scoring for Coventry.
Speaking immediately after the match, former Manchester City manager Hughes was hopeful he would be given more time to lift Stoke out of the relegation zone.
“The fact we’ve gone out, even if it’s a little bit raw at the moment, might help us,” he said.
“Has it changed anything (his future) markedly from this afternoon? Is it any different from the situation after the Newcastle game? I don’t think it is. It just highlights we need to do better.
“But in the long term, certainly until the end of the season, it might be a blessing for us.”
But Stoke’s hierarchy have decided they must act to avoid the club plunging into the Championship.
Hughes looked to be on borrowed time when he rested all his established players for a 5-0 defeat at Chelsea in a bid to keep them fresh for a match against Newcastle.
However, Stoke lost to Newcastle, despite Hughes restoring the key players to his starting line-up, in a damaging result that triggered an avalanche of criticism for the former Manchester United striker.
Hughes, who was appointed as the replacement for Tony Pulis in 2013, leaves with Stoke in the bottom three on goal difference after winning only one of their last seven league games.
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