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.
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.
“I was literally thinking I’d need surgery but I talked to Greg, he was like no, no, no, don’t do any of that, we’re going to teach your body to tolerate the force. Usually when ligaments get torn or bones get broken or whatever it’s because the muscles aren’t functioning properly, so thats what I’ve been doing.” He’s been focusing on exercises that get him into “extreme positions of rotations and flexions” at which point he adds weight to build mental and physical tolerance in those positions.
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.
In 2008, Fowler repeated as Sunnehanna Amateur champion. In the first round of the U.S. Open, Fowler shot a −1 (70) and was in a tie for 7th place. He was one of three amateurs to make the cut, along with Derek Fathauer and Michael Thompson. He ended the tournament tied for 60th. In October 2008 Fowler played on the Eisenhower Trophy team that finished second. He was the leading individual player.
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.
On July 16, 2017, DeChambeau earned his first PGA Tour victory by winning the John Deere Classic by a single stroke over Patrick Rodgers. He carded a round of 65 in the final round to win his maiden title in his 40th start on tour. The win coming the week before, gained DeChambeau a place in the 2017 Open Championship, where he missed the cut after rounds of 76–77 (+13).
On 28 January 2010, Lowry agreed a deal which would take him on a loan to Leeds United until 13 March 2010, joining his fellow Australian international teammates Patrick Kisnorbo and Neil Kilkenny. He made his debut for Leeds against Colchester United, playing left back for Leeds. After an impressive debut, Lowry suffered a minor injury and had to be substituted and replaced by Bradley Johnson after 70 minutes. After missing the FA Cup replay against Tottenham Hotspur due to not being eligible, Lowry returned to the Leeds starting lineup in the following game against Hartlepool United.
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.
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.
The Open Championship: Playing in the final group Sunday for the second straight time in a major championship, made a solid bid for the title, at The Open Championship, with a final-round, 5-under 67. Along with Garcia, finished second to Rory McIlroy by two strokes. With his finish at Royal Liverpool GC, became the only player of the season to claim top-five finishes in the year's first three major championships. He also became the first player to claim top-10 finishes in a season's first three majors since Woods achieved the feat in 2005. His T2 at Royal Liverpool supplanted his previous-best Open Championship finish (in four starts) of T5 in 2011. Rounds of 69-69-68-67 made him the only player in the field to post all four rounds in the 60s.
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.
Presidents Cup: Closed out his second consecutive Presidents Cup appearance with a 6-and-4 victory over Emiliano Grillo, helping lead the United States to a 19-11 win over the International Team. Compiled a 3-0-1 overall record, highlighted by victories the first two days with teammate Justin Thomas in Foursomes (6 and 4 over Charl Schwartzel and Hideki Matsuyama) and Four-ball (3 and 2 over Branden Grace and Louis Oosthuizen).
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.
Waste Management Phoenix Open: Won fifth PGA TOUR title at the Waste Management Phoenix Open in his 220th career start at the age of 30 years, 1 month, 21 days. Began the final round with a four-shot lead and won by two strokes after recording a double bogey and triple bogey en route to a closing 3-over 74. Became the first player since 1983 to win with both a double bogey and triple bogey or worse in the final round. Triple bogey came at No. 11 at TPC Scottsdale after he chipped his ball into the water and received an additional penalty when the ball rolled back into the water after he had placed it back into play. Marked the second time of seven occasions he converted a 54-hole lead to victory.
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.
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.