Roma are ninth in the league after Sunday's 3-1 loss to AC Milan and have struggled to overcome the loss of key players due to injury, including striker Paulo Dybala.
"AS Roma can confirm that Jose Mourinho and his coaching staff will leave the club with immediate effect," the club said in a statement.
"Further updates on the new first team coaching staff will follow imminently."
Mourinho, who has coached a host of top European clubs including Porto, Chelsea, Inter Milan, Real Madrid and Manchester United, was appointed coach of Roma in 2021.
Mourinho was in his third season at Roma and his contract was due to expire in June.
He led the Giallorossi to the UEFA Conference League title in his first season and Roma were Europa League finalists last season.
But Mourinho was also given a series of bans for his protests and tirades against referees, which was clearly not appreciated by Roma's American owners.
Owners Dan and Ryan Friedkin added: "We would like to thank Jose on behalf of all of us at AS Roma for his passion and efforts since his arrival at the club.
"We will always have great memories of his tenure at Roma, but we believe that an immediate change is in the best interests of the club.
"We wish Jose and his assistants all the best in their future endeavours."
with AP/PA
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