Fowler's first PGA Tour event as a professional was the Justin Timberlake Shriners Hospitals for Children Open where he finished tied for seventh. His second PGA Tour event was at the Frys.com Open played at Grayhawk Golf Club in Scottsdale, Arizona. He finished tied for second after losing to Troy Matteson in a three-way playoff that included Jamie Lovemark. Fowler's score of 18-under-par included a hole-in-one on the fifth hole in his final round. Fowler also notched an eagle in each of his four rounds.
Nationwide Tour Players Cup: Playoff runner-up to Derek Lamely at the Nationwide Children's Hospital Invitational. Started the final round five shots behind 54-hole leader Dave Schultz. Held the lead during much of the final round but suffered a bogey at the 72nd hole of regulation to drop into a tie with Lamely and force a playoff. Lost to Lamely when he failed to get up and down from a greenside bunker on the second extra hole, missing his par putt of 12 feet. Lamely rolled in a three-foot par putt to win.
OHL Classic at Mayakoba: Birdied two of his last three holes at the OHL Classic at Mayakoba to fire a final-round 67 and finish in 2nd place, one shot back of Patton Kizzire. In his first start at the event, opened with a bogey-free, 6-under 65 to sit three back of Kizzire's lead. Followed with three-consecutives rounds of 67 in rounds two through four, resulting in a score of 18-under 266. Due to inclement weather Saturday, played his final two rounds on Sunday.
Quicken Loans National: Starting the final round of the Quicken Loans National seven shots back, the Quicken Loans ambassador recorded a career-best nine birdies to post his low round of the week, a 5-under 65 to finish T3. Marked his third top-five in his last four starts. Chances for victory took a serious hit with a double bogey (the only one of the final round) on No. 14, the easiest hole in the final round. Marked second top-three finish in six starts at the Quicken Loans National (2015-2nd).
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"
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.
Aberdeen Asset Management Scottish Open: Earned his second international victory when he captured the Aberdeen Asset management Scottish Open in come-from-behind fashion at Gullane GC in July. After a bogey on the 14th hole Sunday, fell two shots off the lead. He responded with three birdies over his final four holes to catch and pass American Matt Kuchar, who shot a final-round 68 to post the clubhouse lead at 11-under. He made a 9-foot birdie putt at No. 15, made a two-putt birdie at the par-5 16th, parred the 17th then hit his approach shot on the par-4 finishing hole to 2 feet for the tap-in birdie and the title. Joined seven other players who made the Scottish Open their first European Tour win.
Lowry missed the first three cuts of his professional career, but had his first payday on 5 July, when he finished 50th at the Open de France ALSTOM. He had his best professional result in November 2009, when he finished 3rd in the Dunlop Phoenix Tournament in Japan. In January 2010, Lowry finished in fourth place in the Abu Dhabi Golf Championship, moving him into the top-100 of the Official World Golf Ranking.
U.S. Open: Playing alongside eventual-champion Martin Kaymer in the final pairing Sunday, followed up his career-best round (3-under 67) in a U.S. Open with a final-round, 2-over 72 to remain T2 (the sixth runner-up finish of his career). It was his best performance in six U.S. Open starts (previous-best finish was a T10 in 2013). It was also his top major championship showing among his 18 starts (previous-best finishes were T5s at the 2011 Open Championship and the 2014 Masters). His pairing with the 29-year-old Kaymer was just the third final grouping at the U.S. Open since 1965 with two players in their 20s. The others were John Mahaffey (28) and Jerry Pate (22) in 1976 and Woods (26) and Sergio Garcia (22) in 2002.
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.