Playing with his brother Edoardo, they won the 2009 Omega Mission Hills World Cup, Italy's only win in the event.

Molinari won the 2010 WGC-HSBC Champions and has represented Europe in three winning Ryder Cup teams, in 2010, 2012 and 2018.

In May 2006, Molinari claimed his first European Tour victory, becoming the first Italian since Massimo Mannelli in 1980 to win the Telecom Italia Open.

In October 2010, Molinari represented Europe in the 2010 Ryder Cup which took place at Celtic Manor Resort, teaming up with his brother Edoardo in the four-balls (halved against Stuart Cink and Matt Kuchar) and foursomes (lost against Zach Johnson and Hunter Mahan).

Molinari picked up his third win on the European Tour on 6 May 2012 at the Reale Seguros Open de España.

Molinari gained an automatic selection for the 2012 Ryder Cup, where he played the foursomes with Lee Westwood on Friday, losing by 3 and 2 to Jason Dufner and Zach Johnson; he then teamed up in the four-balls with Justin Rose, losing by 5 and 4 against Bubba Watson and Webb Simpson.

[9] During the 2013 and 2014 seasons Molinari did not register a tournament win, but his steady position in the top fifty of the OWGR allowed him to play several PGA Tour events as a non-member, where he reached three top ten finishes; among these the most prestigious result was the 6th place at the 2014 Players Championship.

At the 2018 Open Championship, Molinari won the tournament with a score of −8, pairing with Tiger Woods in the final round.

[15] On 10 March 2019, Molinari won the Arnold Palmer Invitational for his third PGA Tour victory of his career.

He teed off 10 groups ahead of the leaders on the final day and 5 stokes behind, making three birdies and no bogeys on his first seven holes.

[16] In April 2019, Molinari was the 54-hole leader at the Masters at 13 under, two strokes clear of Tony Finau and Tiger Woods, after a six-under-par 66 third round.

Molinari held the lead for two thirds of the final round, until he reached the par-3 12th, where his tee shot found the water, resulting in a double bogey.

1Cancelled due to COVID-19 pandemic QF, R16, R32, R64 = Round in which player lost in match play NT = No tournament "T" = Tied ^ Molinari became member of the PGA Tour in 2015, so he is not included in the money list before that.