Hughes was given his marching orders after watching his side slump to a 2-1 defeat at Coventry in the third round of the FA Cup on Saturday.
"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 was appointed at Stoke on May 30, 2013, taking over from fellow Welshman Tony Pulis.
He leaves the club 16th in the Premier League standings and with only one win in their last eight games in all competitions.