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.
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.
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.
THE PLAYERS Championship: A week after collecting his first PGA TOUR victory, nearly became the first player since David Duval (1997) to post first two TOUR victories in back-to-back weeks, finishing T2 at THE PLAYERS, two strokes behind winner Matt Kuchar. Holed a birdie attempt from 21 feet, 7 inches on the par 3 17th in the final round to move to 11-under but couldn't convert a 7-foot, 7-inch birdie on No. 18 that would have given him the clubhouse lead at 12-under. Recorded his fifth career runner-up finish on TOUR in his 73rd start. His T2 performance came in his third start at THE PLAYERS and first in which he made the 36-hole cut. Moved into contention with a 66 in the third round, a career low at TPC Sawgrass. Entered the final round three shots off the 54-hole pace.
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.
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.
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.
Lowry made his Leyton Orient debut, playing as a left-back position, in the opening game of the season, which saw Leyton Orient lost 2–1 to Chesterfield. Since his debut, Lowry established himself in the left-back position in the first half of the season despite being sidelined with suspension and fitness concern that saw him out for two matches. Following his return to the first team, Lowry played in the central-defense between December and March until he dropped from the first team throughout March. Lowry went on to make his first team return throughout 2014–15 season, making thirty-four appearance in his first season at Leyton Orient.
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.
2019 Open Champion Shane Lowry, compared to Tommy Fleetwood, is on the other side of the spectrum in regards to brand loyalty. He is Cleveland/Srixon in 12 clubs including the ball with the only two exceptions being the TaylorMade M4 3-wood and his Odyssey Putter. In this case, that makes sense, those clubs seem to be a challenge to swap, especially the 3-wood, and Cleveland/Srixon isn’t really known for putters on the PGA Tour.
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"