Lowry started his youth career with Australian club ECU Joondalup. He signed for Aston Villa in February 2005 along with fellow Australian Chris Herd. Lowry made nine appearances for Aston Villa Reserves in the 2006–07 season, mainly coming near the end of the campaign. Lowry was also part of the squad that won the HKFC International Soccer Sevens in May 2007. In June 2007, Lowry signed a 12-month deal to his contract.
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 started the 2018-19 season with partial status after finishing 140th in the FedEx Cup. He moved into a share of the 36-hole lead at the 2019 Open Championship at Royal Portrush, after successive opening rounds of 67. He was tied at eight under with J. B. Holmes. Lowry then shot a 63 for a new course record to lead by four strokes at the end of the third round. He won the tournament by six shots ahead of Tommy Fleetwood.
On 23 November 2011, Lowry was again loaned out to play in the Championship, this time to Millwall until 3 January 2012. He followed Aston Villa team-mate Nathan Baker who also signed on loan for Millwall two days earlier. Lowry made his Millwall debut three days later, where he played 90 minutes, in a 0–0 draw against Crystal Palace. His impressive display at Millwall soon earned a loan extension. Weeks later on 13 January 2012, Lowry was sent-off in the 22nd minutes after stamping on Nikola Žigić, which saw Millwall lose 6–0. Three years on after signing for Birmingham City, Lowry stated, quoting: "Whatever club I play for I fully commit to that club at the time. I play with my heart on my sleeve. Sometimes in the past I have gone overboard but I was a younger player then, I have learned a lot from these types of experiences. But I am an aggressive player, that’s the way I like to play and I can’t change the way I play. I will use my experience now and be a bit more clever."'
The Honda Classic: After beginning the final round of The Honda Classic with a four-stroke lead, posted a 1-over 71 to win by the same margin for his fourth career PGA TOUR title. It marked the first of five 54-hole leads he converted to victory. Opened with back-to-back 66s for the second consecutive year and posted a 65 in the third round to post the best 54-hole total since the event moved to PGA National in 2007 at 13-under 197. Seized the 54-hole lead with the widest margin of his career entering a final round. Turned in 2-over 37, but posted three birdies on the back nine to take command of the tournament. Despite bogeys on the 71st and 72nd holes, claimed his first victory since the 2015 Dell Technologies Championship. Finished the week second in Strokes Gained: Putting (7.392) and moved to 10th in the FedExCup standings and ninth in the Official World Golf Ranking, his first time in the top 10 since the 2016 BMW Championship.
U.S. Open: Established the first-round lead at the U.S. Open with a 7-under 65 and was in the mix all week at Erin Hills. Followed with 73 to be one back through 36 holes. Third-round 68 had him two adrift headed into final round. Closed with even-par 72 to finish six back of Brooks Koepka at T5. In nine U.S. Open appearances, has advanced to the weekend five times and never broken par in the final round.
The Barclays: Held a one-stroke lead over Patrick Reed after 54 holes at The Barclays in the FedExCup Playoffs, before a double bogey-birdie-bogey finish on Nos. 16-18 resulted in a T7 at 6-under 278 with Jason Kokrak and Ryan Moore. Fowler went bogey free at Bethpage Black from the 10th hole in round one until the 11th hole in the final round, a span of 55 holes. His 55-consecutive holes without a bogey became a personal best on the PGA TOUR, besting 53 from the 2010 Memorial Tournament. This streak also marked the longest recorded in Barclays history since hole information began in 1983. Ian Poulter had the longest with 45 in 2010. The finish marked his third top-10 showing in his last four starts in the event (T9/2013, T9/2014).