The former Chelsea and Manchester United manager leaves the Serie A club in ninth place after defeat to AC Milan.
Jose Mourinho has been sacked by Roma, ending his spell in Italy during its third season.
The Italians have moved quickly to replace the Portuguese, hiring legendary player Daniele De Rossi as head coach until the end of the season.
Mourinho joined the Giallorossi in 2021 and won the Europa Conference League in 2022, before guiding the team to the Europa League final last season.
But defeat to Milan last weekend leaves the club in ninth in Serie A, and with his contract set to expire this summer, the club has made the decision to make a change.
A club statement read: “We would like to thank José on behalf of all of us at AS Roma for his passion and efforts since his arrival at the club,” said 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 José and his assistants all the best in their future endeavours.”
Mourinho was not in the dugout for his final match against the Rossoneri, with goals from Yacine Adli, Olivier Giroud and Theo Hernandez condemning his side to defeat.
Two red cards in Roma’s last matches ensured Mourinho was handed a touchline ban, with fans booing him when he appeared on the screen at the San Siro.
Roma forward Andrea Belotti conceded the team had hit “rock bottom,” telling DAZN: “It is clear that we are struggling, because when you come off certain defeats, you cannot be happy or relaxed.
“We lost the derby and there is a great deal of frustration at the way that went. Now we have some time to get sorted out physically and mentally, but also to try out some tactical movements on the training ground. We feel like we hit rock bottom right now, but it does mean the only way is up.”
Roma host Verona on Saturday, with the side five points off a fourth-placed Fiorentina and a Champions League place.
Mourinho’s progress this season has been hindered by injuries, with Tammy Abraham out with an anterior cruciate ligament injury and Chris Smalling also recovering from a knee problem.
Paulo Dybala was absent against Milan, while Houssem Aouar and Evan Ndicka are away at the Africa Cup of Nations and Sardar Azmoun is playing at the Asian Cup.