The news is a boost for Tottenham, who placed Mourinho on gardening leave following his sacking last month, less than a week before their Carabao Cup Final defeat to Man City.
Spurs were reported to have agreed a compensation package in the region of £15million with the 57-year-old but that figure could be significantly reduced now that he has found a new job.
Mourinho was dismissed with Spurs languishing in seventh-place in the Premier League and amid growing discontent about the style of football under the Portuguese.
But Roma’s general manager Tiago Pinto said the club could miss the opportunity to hire one of the game’s all-time great coaches, who has signed a deal until 2024.
“When José became available, we immediately jumped at the chance to speak with one of the greatest managers of all time,” said Pinto.
“We were blown away by José’s desire to win and his passion for the game: no matter how many trophies he has won, his primary focus is always on the next one. He possesses the knowledge, experience and leadership to compete at all levels.
“We know that in order to build a successful sporting project it takes time, patience and the right people in the right positions. We are supremely confident that José will be the perfect coach for our project, for both our immediate and long-term future.
“Together with the vision and ambition of [owners] Dan and Ryan Friedkin, we will build the foundations of a new AS Roma.”
Spurs were the first club in Mourinho illustrious career where he failed to win silverware, and they were knocked out of the Europa League in humiliating fashion by Dinamo Zagreb this season.
The former Porto, Chelsea, Inter Milan, Real Madrid and Manchester United boss said Roma’s ambition and the passion of their supporters persuaded him to make a quick return to the dugout.
“After meetings with the ownership and Tiago Pinto, I immediately understood the full extent of their ambitions for AS Roma,” said Mourinho.
“It is the same ambition and drive that has always motivated me and together we want to build a winning project over the upcoming years.
“The incredible passion of the Roma fans convinced me to accept the job and I cannot wait to start next season.
“In the meantime, I wish [my predecessor] Paulo Fonseca all the best and I hope the media appreciate that I will only speak further in due course. Daje Roma!”
In an interview published only last week, Mourinho said he had “no plans” in place regarding his next job and suggested returning to management next season could be “premature”.
However, on Tuesday afternoon a Roma club statement confirmed his appointment, saying: “The club are delighted to announce an agreement has been reached with Jose Mourinho for him to become our new head coach ahead of the 2021-22 season.”
Earlier on Tuesday, Roma announced they would be parting ways with current coach Paulo Fonseca at the end of the campaign, with the club having endured a difficult run in the league since the turn of the year.
Their Europa League form had kept them in with a chance of Champions League qualification for next season, but they are now all-but out of that competition after a 6-2 defeat to Manchester United in their semi-final first leg on Thursday.
Jose Mourinho sacked by Tottenham
The move will see Mourinho return to Serie A, where he enjoyed great success while in charge of Inter Milan, winning an historic league, cup and Champions League treble in 2010, as well as the title the previous season.
Mourinho has already lined-up a job as a pundit for radio station talkSPORT during this summer’s European Championship.