Hamilton are looking for a new manager following the sudden departure of Martin Canning.
Chairman Allan Maitland announced in a statement that the 37-year-old had left by "mutual agreement".
The announcement comes exactly seven days after Canning launched a fierce defence of his record, which has seen him keep the club in the Ladbrokes Premiership for a record fifth consecutive season.
Accies have since suffered back-to-back 3-0 defeats against Aberdeen and Celtic to make it five losses in a row. They sit 10th, two points and places above St Mirren and with second-bottom Dundee visiting the Hope Stadium on Saturday.
Former Hamilton manager Maitland, who took over as chairman in December, added in his statement: "With the departure of so many important players over the last two seasons (Michael Devlin, Eamonn Brophy, Lewis Ferguson, Ali Crawford and Greg Docherty) it has become increasingly difficult to maintain the playing levels and results previously reached.
"Martin and the board feel that a change was necessary to give the club the best opportunity to get back to those levels.
"The club would like to thank Martin for his commitment and efforts during his 10-and-a-half years at the club as both a player and a manager.
"He played in over 200 games including the play-off match at Hibs in May 2014 when we secured our place in the Premier League and has managed the club in the top division for the last four seasons.
"He has successfully managed to maintain our status in the Premier League and we will be forever grateful for his part in this achievement."
Canning defended his performance seven days earlier after abuse from fans prompted his father, nephew and uncle to leave Hamilton's William Hill Scottish Cup defeat by St Johnstone before half-time.
"It's not often that I defend myself, I usually just accept it and move on, keep my head down and work hard," Canning said last Tuesday.
"But my job is to keep Hamilton in the Premiership. Every year we are tipped to go down, every year we fight extremely hard to stay up, and we have kept the club up four times. That's our record, we have never done that before in our history. That's success.
"My job is to bring young players into the first team and move them on. Since I've been the manager, Stephen Hendrie has moved, Michael Devlin has moved, Lewis Ferguson has moved, Greg Docherty has moved. The club have earned good money from these moves.
"That's exactly what we are asked to do and we are doing that. But fans want to win, I want to win, we all want to win, and it becomes difficult.
"If someone had said you'd be on 14 points at this stage of the season but there would be two teams below you, I would have taken that."
First-team coach Guillaume Beuzelin and academy director George Cairns have been placed in charge "until further notice", while Under-18s coach Jason Scotland has also left the club.
