Molinari made eight birdies, including a 44-foot putt on the 18th hole, to pick up his third PGA Tour victory.
For the second straight year at Bay Hill, a final-round 64 posted well before the final group finished was good enough for the trophy.
A year after Rory McIlroy surged to win the Arnold Palmer Invitational, Francesco Molinari fired a round of eight birdies—including a dramatic 44-footer on the 18th hole—to win his third PGA Tour event in eight months.
Molinari started the day five behind 54-hole leader Matthew Fitzpatrick, who finished second at 10 under. But the reigning British Open champion got off to an ideal start, making four birdies on the front nine to turn in 32 and put himself square in contention. He added birdies at 12, 13 and 16 to take the solo lead before dropping the dramatic putt on the 72nd hole.
"High up there with the best wins I've had," Molinari said. "Arnie was a special player but more importantly a special person
Sungjae Im, Tommy Fleetwood and Rafa Cabrera Bello finished in a three-way tied for third at nine under.
Rory McIlroy, who started the day just one back, finished a shot further back in a tie for sixth. It was the third time this year that McIlroy has played in the final round of a PGA Tour event, but he has yet to win despite finishing in the top 10 in all five starts this season. Since his last victory, which came last year at Bay Hill, McIlroy has now played in the final pairing of seven events without a victory.
The winner of last week's Honda Classic, Keith Mitchell, also finished at eight under after a final-round 66.