The former Serbia international has signed on at the Stadio Olympico for one year.
This is the third time Roma manager Mourinho has signed Matic, having convinced him to swap Benfica for Chelsea in January 2014 before bringing him to Old Trafford from Stamford Bridge in the summer of 2017.
Matic made 189 appearances for Manchester United in five years at the club but failed to win a trophy.
Speaking following the announcement of his move, Matic said: “I am pleased and honoured to be joining this club and I cannot wait to start the new season with my team-mates.
“Roma is a big club, with amazing fans and a coach, Jose Mourinho, who is well known to everyone – making the decision to come here very straightforward.
“I hope that by working together we are able to achieve some great things.”
Roma's general manager Tiago Pinto added: "The enthusiasm he showed at the prospect of joining our project was hugely encouraging."
"Nemanja brings with him to Roma not just a lot of quality on the pitch, but the vast experience he has gained from so many seasons in the Premier League and a focus and mentality that has consistently set him apart throughout his career."
Roma won the inaugural UEFA Conference League last season and finished sixth in Serie A.
