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.
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.
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.
Wells Fargo Championship: Made birdie-3 on the first extra hole (No. 18) to defeat Rory McIlroy and D.A. Points at the Wells Fargo Championship for his first TOUR win. Improved to 1-1 in playoffs (lost to Troy Matteson, 2009 Frys.com Open). The playoff was the fifth at the Wells Fargo Championship. At the age of 23 years, 4 months, 23 days, became the third player to make the Wells Fargo Championship his first PGA TOUR win (Anthony Kim in 2008 and McIlroy in 2010). Became the third-youngest winner of the event, behind McIlroy (20 years, 11 months, 28 days) and Kim (22, 10, 15). His win came in his 72nd start on TOUR and was his 16th top-10 finish. Opening-round 66 is the lowest start by a winner of the Wells Fargo Championship. Won in his third start at the Wells Fargo Championship (T6 in 2010 and T16 in 2011).
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.
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.
PGA Championship: With his T5 finish at the PGA Championship, finishing three strokes behind champion Justin Thomas, continued to be a top-five machine in major championships, recording his seventh such finish in 32 starts. Made a furious Sunday rally, with six birdies, including four in a row on Nos 12-15, but pars on The Green Mile (Nos. 16-18) left him a few short of his friend, Justin Thomas.
After a T-12 finish at the Masters, Fowler earned his first win in over three years with a playoff victory at The Players Championship in May. Trailing Sergio García midway through the final round by five shots, Fowler played the final six holes in 6-under par, including an eagle at the par-5 16th. After a birdie at the famous 17th hole, Fowler's final birdie of the round on 18 left him at 12-under par. Both García and Kevin Kisner had birdie attempts to win at the 18th in regulation, but both missed and the three men went to a three-hole aggregate playoff to decide a winner on holes 16–18. Fowler and Kisner went par-birdie-par to tie at −1 while García's three pars left him at even and he was eliminated. Thus Fowler and Kisner went to sudden death starting at the 17th, where Kisner's tee shot landed within about 12 feet (3.7 m) of the cup. Fowler answered with a shot inside of five feet, and when Kisner's birdie attempt slid by, Fowler responded by making his short birdie to claim the championship. Fowler played his final 10 holes in 8-under par. On July 12, he won the Aberdeen Asset Management Scottish Open on the European Tour, shooting a 12-under-par 268. On September 7, he won the Deutsche Bank Championship, the second FedEx Cup Playoffs event, by one stroke over Henrik Stenson, for his third victory on the PGA Tour.
BMW Championship: After entering the final round of the BMW Championship in a second-place tie with Jason Day (five strokes behind Marc Leishman), recorded a 4-under 67 to finish T2, his 11th career runner-up on the PGA TOUR. Week was highlighted by a career-best, six consecutive birdies in the first round on Nos. 12-17. Chipped in from 64 feet on the 17th.