Lowry won for the first time as a professional in 2012, at the Portugal Masters in October. He shot a 67 to tie for the lead with the Englishman Ross Fisher, who made bogey on the final hole after missing a four-foot putt. The victory lifted Lowry back into the Official World Golf Ranking top 100 and made him eligible to compete in the WGC-HSBC Champions.
The form and fitness of centre-backs Michael Morrison and Jonathan Spector and left-back Jonathan Grounds restricted Lowry to a seat on the bench until mid-December. He eventually made his debut in the starting eleven for the home fixture against Cardiff City on 18 December, standing in for the injured Grounds at left back. He appeared once more, in the FA Cup, before his contract was cancelled by mutual consent to enable him to return to Australia.
Abu Dhabi HSBC Golf Championship: Held off final-round charges from Thomas Pieters, Rory McIlroy and Henrik Stenson to win the Abu Dhabi HSBC Golf Championship, marking his second European Tour title. The victory was the first at the event by an American since Chris DiMarco won the inaugural event in 2006. Final-round highlights included a holed bunker shot on the eighth hole (which helped propel him to a three-stroke cushion at the turn), a chip-in for birdie on the 17th hole and then a par on the last to hold off Pieters by one stroke.
Waste Management Phoenix Open: Claimed his second runner-up finish at the Waste Management Phoenix Open, one shot behind Hunter Mahan. Had birdie opportunities on the last three holes but unable to catch Mahan. Previously lost in a playoff to Troy Matteson just down the road at Grayhawk GC in the 2009 Frys.com Open. Had he won at TPC Scottsdale, would have become the first Sponsor Exemption to do so since Jason Gore (2005 84 Lumber Classic). Lee Westwood later won in June as a Sponsor Exemption at the St. Jude Classic presented by Smith & Nephew.
BMW Championship: Entered the BMW Championship No. 36 in the FedExCup standings, with his T39 finish at Conway Farms outside Chicago leading to a final ranking of No. 38. Advanced to the TOUR Championship by Coca-Cola in 2012 (finished No. 28 in the FedExCup), but other three seasons led to near misses of cracking the top 30 in the FedExCup (No. 43 in 2011 and No. 32 in 2010).
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.
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.
At the first FedEx Cup playoff event, Fowler finished T52 at The Barclays in the last week in August. The following week he again finished T52 at the Deutsche Bank Championship, the second FedEx Cup playoff event, after carding a disappointing six-over par final round 77. At that point Fowler was positioned 37 in the FedEx Cup points standings and required a strong performance at the BMW Championship to qualify in the top thirty for The Tour Championship; a performance which eluded him, finishing in 48th place. In finishing 43rd in the FedEx Cup, Fowler earned a $132,000 bonus.
In July 2011, Fowler tied the 54-hole lead at the AT&T National, but an early double bogey on Sunday derailed his opportunity for his first PGA Tour win. Two weeks later Fowler finished tied for 5th in The Open Championship at Royal St George's. In August, Fowler finished in a tie for second at the WGC-Bridgestone Invitational behind winner Adam Scott, lifting him to 28 in the world rankings.
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.
On 23 November 2011, Lowry was again loaned out to play in the Championship, this time to Millwall until 3 January 2012. He followed Aston Villa team-mate Nathan Baker who also signed on loan for Millwall two days earlier. Lowry made his Millwall debut three days later, where he played 90 minutes, in a 0–0 draw against Crystal Palace. His impressive display at Millwall soon earned a loan extension. Weeks later on 13 January 2012, Lowry was sent-off in the 22nd minutes after stamping on Nikola Žigić, which saw Millwall lose 6–0. Three years on after signing for Birmingham City, Lowry stated, quoting: "Whatever club I play for I fully commit to that club at the time. I play with my heart on my sleeve. Sometimes in the past I have gone overboard but I was a younger player then, I have learned a lot from these types of experiences. But I am an aggressive player, that’s the way I like to play and I can’t change the way I play. I will use my experience now and be a bit more clever."'
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.
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.
In June 2015, he became the first SMU Mustang to win the NCAA individual championship, recording a score of 280 (−8) to win by one stroke. In August, he won the U.S. Amateur title, defeating Derek Bard 7 & 6 in the 36-hole final. He became the fifth player to win both the NCAA and U.S. Amateur titles in the same year, joining Jack Nicklaus (1961), Phil Mickelson (1990), Tiger Woods (1996), and Ryan Moore (2004).
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.
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.
In the 2013–14 season, Lowry suffered a minor thigh strain in the club's pre-season friendly. Despite this, Lowry remained in the first team under the new management of Steve Lomas until he received a straight red card after a foul on Will Hughes, in a 5–1 loss against Derby County on 14 September 2013. After serving a three match ban, Lowry remained on the bench without playing for four matches Lowry made his first team return on 2 November 2013 when he came on as a substitute for Scott Malone against Burnley. However, his return, after spending two months without playing, was a disastrous when he scored an own goal, which saw Millwall drew 2–2. After this, Lowry was out of the first team, demoted to the substitute bench between mid-November and mid-December until he made his return on 26 December 2013, in a 4–0 loss against Watford. On 28 January 2014, Lowry was sent-off for the second time this season in the late-minutes against Sheffield Wednesday after fighting with Giles Coke, who also was sent-off as well, with both side drew 1–1. After serving a four match ban, Lowry was in the first team throughout February and March until he suffered a foot injury that kept him out for the remainder of the season. Lowry went on to finish the 2013–14 season, making twenty-two appearance.
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.
At the first FedEx Cup playoff event of the season, The Barclays, Fowler went into the final round leading the event by one stroke. He endured a difficult final round, shooting a two-over-par 74. His challenge was ended with a double-bogey at the 16th hole that put him four strokes behind playing partner Patrick Reed. He went on to finish T7, three strokes behind the winner Reed. As a result of this, Fowler also failed to secure his automatic Ryder Cup spot, which he would have done with a top-three finish. Fowler moved up from 28th to 16th in the FedEx Cup standings with this result.
Lowry did not win on the European Tour from 2016 to 2018 but was joint runner-up in the 2017 DP World Tour Championship, Dubai and runner-up in the 2018 Andalucía Valderrama Masters. In January 2019 he won the Abu Dhabi HSBC Championship by a stroke from Richard Sterne. Lowry led by 3 strokes after three rounds but was two-over-par after 11 holes of his final round and dropped 4 shots behind Sterne. However he finished with 3 birdies in the final 7 holes, while Sterne had two bogeys, giving Lowry the victory.
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.