In May 2012, Fowler won the Wells Fargo Championship in Charlotte on the first extra hole of a sudden-death playoff. Replaying the 18th hole, he defeated Rory McIlroy and D. A. Points with a birdie to gain his first PGA Tour win. Fowler shot a 69 (−3) in the final round to finish in a three-way tie after 72 holes at Quail Hollow Club. This win enabled Fowler to break the top-25 in the world, placing him at number 24. The following week at The Players Championship in Ponte Vedra Beach, Florida, Fowler played the final hole at −11 under par and had a birdie opportunity to bring him within one of leader and eventual winner Matt Kuchar. Fowler, however, pushed his putt to the right and finished in a tie for second, the fifth second-place finish of his career.
Waste Management Phoenix Open: Won fifth PGA TOUR title at the Waste Management Phoenix Open in his 220th career start at the age of 30 years, 1 month, 21 days. Began the final round with a four-shot lead and won by two strokes after recording a double bogey and triple bogey en route to a closing 3-over 74. Became the first player since 1983 to win with both a double bogey and triple bogey or worse in the final round. Triple bogey came at No. 11 at TPC Scottsdale after he chipped his ball into the water and received an additional penalty when the ball rolled back into the water after he had placed it back into play. Marked the second time of seven occasions he converted a 54-hole lead to victory.
Lowry elected to turn professional the week after his Irish Open triumph, meaning that he would miss out on the opportunity to play in the Walker Cup in September 2009. He made his professional début on 28 May at the European Open, where he shot 78 in the first round to end the opening day almost at the back of the field, and went on to miss the cut following a second round 73.
“I was literally thinking I’d need surgery but I talked to Greg, he was like no, no, no, don’t do any of that, we’re going to teach your body to tolerate the force. Usually when ligaments get torn or bones get broken or whatever it’s because the muscles aren’t functioning properly, so thats what I’ve been doing.” He’s been focusing on exercises that get him into “extreme positions of rotations and flexions” at which point he adds weight to build mental and physical tolerance in those positions.
On 27 January 2016, Lowry returned to Australia after a decade away from Australia when he signed a two-and-a-half-year deal with A-League side Perth Glory. Upon joining Perth Glory, Lowry said of the move, quoting: "I've got a lot of experience behind me now and I want to use it to guide the young lads who are in this young squad. I've spent 11 years in England and it's shaped my football over there and I'm really happy to be here and get stuck into the games"