Roma s midfielder French Jordan Veretout (L) fights for the ball with Inter Milan s Italian midfielder Nicolo Barella (R) during the Italian Serie A football match between Inter Milan and AS Roma on April 23, 2022 at the San Siro stadium in Milan. AFP
Denzel Dumfries, Marcelo Brozovic and Lautaro Martinez scored for Inter and Henrikh Mkhitaryan netted a late consolation.
Inter moved a point above AC Milan, which faces a tricky trip to Lazio on Sunday.
It was the third straight match in which Inter scored three, having done so at Spezia last weekend in the league and on Tuesday in the Italian Cup semifinal against Milan.
Roma's first loss in 12 league matches left it five points behind fourth-placed Juventus.
It was Mourinho's first return to Inter as an opposing coach since he left the club in 2010 after steering it to the treble of the Italian league, Cup and Champions League. Inter beat Roma 3-0 in the Italian capital in December.
Roma almost broke the deadlock in the 29th minute but Gianluca Mancini headed a free kick just wide of the top right corner.
Instead, it was Inter which took the lead moments later as Dumfries ran onto a delightful through-ball from Hakan Calhanoglu and slotted it between the legs of the onrushing Roma goalkeeper Rui Patricio.
Inter doubled its lead five minutes from halftime with a splendid goal from Brozovic, who cut inside and beat Chris Smalling before curling into the top right corner.
And the match was all but over seven minutes after the break when Martinez was left unmarked to head in a corner from close range.
Despite the scoreline, Mourinho was still able to give a small smile and a wave when the Inter fans sang his name in the 72nd minute.
Roma pulled one back when Eldor Shomurodov cut the ball back for a fierce Mkhitaryan strike into the top right corner.
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