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.
BMW Championship: At No. 22 in the FedExCup standings heading into the third Playoffs event, the BMW Championship, he bogeyed No. 17 in a final-round even-par 72 to miss advancing to the TOUR Championship by half a point, finishing the season No. 31 in the FedExCup standings. Charl Schwartzel fired a final-round 8-under 64 to claim the No. 30 position.
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.
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.
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.
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 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 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.
OHL Classic at Mayakoba: Birdied two of his last three holes at the OHL Classic at Mayakoba to fire a final-round 67 and finish in 2nd place, one shot back of Patton Kizzire. In his first start at the event, opened with a bogey-free, 6-under 65 to sit three back of Kizzire's lead. Followed with three-consecutives rounds of 67 in rounds two through four, resulting in a score of 18-under 266. Due to inclement weather Saturday, played his final two rounds on Sunday.
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.