"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," said owners Dan and Ryan Friedkin.
"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."
The 60-year-old Portuguese took over in 2021 and guided Roma to the inaugural Europa Conference League trophy in 2022 and the final of last season's Europa League.
However Roma have struggled this campaign and currently sit ninth in Serie A, five points away from the Champions League positions, after being convincingly beaten 3-1 at AC Milan on Sunday.
Italian media report that former Roma captain Daniele De Rossi, a World Cup winner with Italy in 2006, could replace Mourinho as coach.