The 28-year-old forward joins the Giallorossi after their sixth-place finish in Serie A in Mourinho’s first season in charge where they also won the UEFA Conference League.
Dybala had spent seven years with Juventus but had made it clear months ago that he would depart the club.
He had been linked with Inter Milan and Napoli but ultimately Roma won the race.
“The days that led me to this signing were a combination of many emotions: the determination and the speed with which Roma showed they wanted me made the difference,” Dybala said.
“I am joining a growing team, with a club that continues to lay ever more solid foundations for the future and a coach, Jose Mourinho, with whom it is a privilege to be able to work.
“As an opponent I admired the atmosphere created by the Giallorossi fans, I can’t wait to greet them with the Roma shirt on.”
Dybala is a five-time Serie A champion who netted 115 goals in 293 games for the Bianconeri.
Roma general manager Tiago Pinto said: “Paulo is a world-renowned player who has won major trophies and gained global acclaim; he will bring that class with him to Roma and I am sure that, with him in the squad, we will be even stronger and more competitive.”
The Argentina international has joined the Roma squad for their pre-season camp in Portugal.
Roma commence the new Serie A season away to Salernitana on August 14.