Lowry made his professional debut in the 2009–10 UEFA Europa League in an away fixture at Rapid Vienna. On 17 September 2009, Lowry signed a three-month loan deal with Football League Championship side Plymouth Argyle. Lowry made his Plymouth Argyle debut on 19 September 2009, playing 90 minutes, in a 3–1 loss against Newcastle United. He played 13 league games for Plymouth during his loan spell, where he impressed many and was recalled by Villa who required Lowry's services as cover after some injuries to defenders.
U.S. Open: Established the first-round lead at the U.S. Open with a 7-under 65 and was in the mix all week at Erin Hills. Followed with 73 to be one back through 36 holes. Third-round 68 had him two adrift headed into final round. Closed with even-par 72 to finish six back of Brooks Koepka at T5. In nine U.S. Open appearances, has advanced to the weekend five times and never broken par in the final round.
Lowry started the 2018-19 season with partial status after finishing 140th in the FedEx Cup. He moved into a share of the 36-hole lead at the 2019 Open Championship at Royal Portrush, after successive opening rounds of 67. He was tied at eight under with J. B. Holmes. Lowry then shot a 63 for a new course record to lead by four strokes at the end of the third round. He won the tournament by six shots ahead of Tommy Fleetwood.
Lowry received his first call-up to the full Australia squad for a friendly against the Netherlands in Sydney and the Asian Cup qualifier against Oman in Melbourne in October. He did not play in either match. On 11 May 2010 he was selected as part of Pim Verbeek's 30-man provisional squad for the 2010 World Cup, and travelled to South Africa, but was not included in the final 23-man World Cup squad. Lowry was named in Han Berger's 18-man squad for an August 2010 friendly against Slovenia, but he did not appear in the match.
Hyundai Tournament of Champions: Finished T6 in a Monday-start-Tuesday-finish event, the season-opening, 54-hole Hyundai Tournament of Champions. The event "started" twice during the regularly scheduled first round Friday and later Sunday, but both times PGA TOUR rules staff halted play due to unplayable windy conditions and subsequently voided all scores that had taken place. As the first player off the tee, he ended up hitting three "opening" shots of the season.
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.