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.
Frys.com Open: At the Frys.com Open in Scottsdale, Ariz., reached a three-way playoff with Jamie Lovemark and eventual-winner Troy Matteson. Began the final round four strokes behind Matteson, but played his first five holes in 5-under, punctuated by a hole-in-one from 211 yards at the par-3 fifth hole. After finishing T2 in the playoff, he had recorded all eight of his professional rounds in the 60s. Thanks to the T7 in Las Vegas at the Justin Timberlake Shriners Hospitals for Children Open and T2 finish at Grayhawk GC, he surpassed No. 150 from the 2008 money list, earning special temporary membership on TOUR for the remainder of the season.
Lowry started for Leeds in the Football League Trophy Northern Area Final, second leg game against Carlisle United, in which the game was lost with Lowry missing the decisive penalty in sudden death in the penalty shootout. After the game it appeared as though Lowry was attacked by a set of Carlisle supporters who had invaded the pitch. After starting every game for Leeds Lowry was dropped from the Leeds squad for the match against Brentford after suffering an injury, before returning to Villa when his loan spell ended. On 25 March 2010 Lowry re-signed for Leeds for a second loan spell, with his loan lasting until the end of the season. Lowry started at left back for Leeds against Norwich City on his return to the club, a match Leeds went on to lose 1–0 in injury time. Lowry didn't overley impress the Leeds fans in his loan spell at Leeds, with him being mostly played out of position at Left back for the entire spell, he was substituted for Jonathan Howson in the final game of the season against Bristol Rovers with 1–0 down at the time, but his loan spell ended on a high as Leeds were promoted in 2nd place after scoring two goals to go on and beat Bristol Rovers and secure promotion to The Championship.
the Memorial Tournament presented by Nationwide: Erased a five-stroke deficit in the final round and briefly held the lead before eventually shooting a final-round 70 to finish runner-up in the Memorial Tournament, three shots behind Jason Dufner. Hit a 350-yard drive on the 72nd hole and had just 136 yards to the pin when play was called for inclement weather for the second time during the final round. When play restarted, he made a costly bogey at the last to fall into a tie for second. Ranked No. 1 in fairways hit for the week with 45 of 56. Was also 8 of 11 in sand saves to rank first for the week.
At the 2016 U.S. Open at Oakmont Country Club near Pittsburgh, Lowry shot 65 (−5) in the third round for 203 (−7) and a four-stroke advantage over Dustin Johnson and Andrew Landry at the 54-hole stage. The 65 was Lowry's joint career best round at a major championship. Due to weather delays on Thursday, the third round was not completed until early on Sunday, and Lowry birdied two of his remaining four holes to extend his two stroke overnight lead to four. In the final round he was in contention for the title, within one shot of Dustin Johnson after 12 holes, before three consecutive bogeys on holes 14, 15 and 16 ended his chances. He finished the tournament tied for second place, with a final round score of 76.
Masters Tournament: Finished runner-up at the Masters, one stroke behind Patrick Reed, for his best result at the event. For the first time in eight starts at Augusta National, recorded four par-or-better rounds (70-72-65-67). Earned his third runner-up in a major (2nd/2018 Masters Tournament, T2/2014 The Open Championship, T2/2014 U.S. Open) and third top-five in the last four (2nd/2018 Masters Tournament, T5/2017 Open Championship, T5/2017 U.S. Open). With third-round 65, was one of just four players to post a bogey-free round during the week (Rory McIlroy/65, Jon Rahm/65, Si Woo Kim/65) with all four occurring 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.
After finishing fifth in the Hyundai Tournament of Champions in Hawaii, Fowler claimed his first victory of 2016 in the Abu Dhabi HSBC Golf Championship on the European Tour. He shot a final round of 69 to finish one clear of Belgium's Thomas Pieters. Two weeks later, Fowler was in contention to win again but lost out to Japan's Hideki Matsuyama in a playoff at the Waste Management Phoenix Open. On March 7, Fowler sparked fantastic scenes after sinking a hole-in-one with fellow tour pro Luke Donald's pitching wedge to win $1 million for Ernie Els' charity, Els for Autism.
Lowry made his debut for the Glory on 30 January 2016, starting against Melbourne Victory. Lowry then scored his first Perth Glory goal on 20 February 2016 when he scored a header in the 41st minutes, to give Brisbane Roar a thrashing with a 6–3 win for Perth Glory. Throughout the 2015–16 season, Lowry established himself in the starting eleven and formed a central defense partnership with Alex Grant, as he made ten appearance for Perth Glory in his first half of the season.
PGA Championship: Finished T3 and two strokes behind McIlroy at the PGA Championship in his 20th major championship start, with T19 in 2013 the previous-best finish in four prior PGA Championship starts. Became the first to claim top-five finishes in all four majors since Woods in 2005. Since 1934, is just the third player to perform the feat, joining Woods in 2000 and 2005 and Jack Nicklaus in 1971 and 1973. Played all four majors in 32-under, with McIlroy second on the list, at 27-under.
Lowry was the 2007 Irish Amateur Close Champion, defeating Niall Turner 4 & 3 in the final. While still an amateur in May 2009, he won The Irish Open on the European Tour, defeating Robert Rock on the third hole of a sudden death playoff. The win, on his tour début, made him just the third amateur to win on the European Tour, following Danny Lee earlier in the 2009 season, and Pablo Martín in 2007. Lowry shot a 62 to equal the lowest ever by an amateur on the circuit and led from the second round onwards.
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.