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.
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.
While serving a suspension, Lowry signed a two-and-a-half-year permanent deal to Millwall for an undisclosed fee on 27 January 2012. Lowry then made his first appearance for the club since joining Millwall permanently, playing 90 minutes, in a 2–1 loss against rivals' West Ham United on 4 February 2012. Right way through March, Lowry was sidelined with ankle injury that kept him out for weeks. After making his first team return against Cardiff City, in a 0–0 draw on 31 March 2012, Lowry scored his first Millwall goal, which he scored the only goal in the game, in a 1–0 win over Coventry City on 17 March 2012. Lowry finished his 2011–12 season, making twenty-two appearance and scoring once.
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.
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.
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.
Quicken Loans National: Starting the final round of the Quicken Loans National seven shots back, the Quicken Loans ambassador recorded a career-best nine birdies to post his low round of the week, a 5-under 65 to finish T3. Marked his third top-five in his last four starts. Chances for victory took a serious hit with a double bogey (the only one of the final round) on No. 14, the easiest hole in the final round. Marked second top-three finish in six starts at the Quicken Loans National (2015-2nd).
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.
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.
As for the workouts he’s doing, DeChambeau is continuing work he’s done with Greg Roskopf, whose system focuses on making people stronger where they are weak, particularly at extraneous points in their muscular system. In other words, there are likely points in the golf swing — in various golf movements — where DeChambeau isn’t as strong as he could be, hence the more work and weight. If he has already ascended to 220 in a matter of weeks, 230 should follow soon. Stay tuned.
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.
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.