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Having already spent a season on loan at the Giallorossi, Mkhitaryan joined on a permanent basis a year ago and was a regular during the 2020-2021 campaign under Paulo Fonseca.
The Armenia international scored 15 goals and provided 11 assists as he made 46 appearances in all competitions, including a run to the Europa League semi-finals that came to an emphatic halt against one of his former teams in Manchester United.
His new deal will see the 32-year-old stay for a further season after embracing life in Rome.
"Over the last two years at Roma I've fallen in love, both with the club and the city, thanks in large part to the incredible passion of the fans," Mkhitaryan said.
"The club's ambitions are very high and I am proud to have the chance to play my part as we take on all the challenges that await us next season. Daje Roma!"
However, Mkhitaryan will no longer be working with Fonseca, the Portuguese coach having been replaced by compatriot Mourinho at the Stadio Olimpico.
Mourinho was in charge at United when the Premier League side signed Mkhitaryan from Borussia Dortmund in July 2016.
The midfielder played in 41 games during his first campaign at Old Trafford but did not make it through the next year. Criticised by Mourinho for his lack of consistency, he joined Arsenal in January 2018 as part of the deal that saw Alexis Sanchez move in the opposite direction.
Now, though, Mkhitaryan and Mourinho are reunited at Roma, who will be playing in the Europa Conference League after finishing seventh in Serie A.