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.
Waste Management Phoenix Open: Two weeks after the win in Abu Dhabi, made his eighth consecutive start in the Waste Management Phoenix Open, where he found himself three strokes off the lead after 54 holes. A final-round 4-under 67, capped off by a clutch birdie on the 72nd hole, forced sudden death with Hideki Matsuyama. On the fourth extra hole, the par-4 17th, an errant tee shot found the water hazard for the second time of the day. Matsuyama made par to win. Ranked second in Strokes Gained: Tee To Green and T1 in Strokes Gained: Total at TPC Scottsdale.
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.
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: Claimed his second runner-up finish at the Waste Management Phoenix Open, one shot behind Hunter Mahan. Had birdie opportunities on the last three holes but unable to catch Mahan. Previously lost in a playoff to Troy Matteson just down the road at Grayhawk GC in the 2009 Frys.com Open. Had he won at TPC Scottsdale, would have become the first Sponsor Exemption to do so since Jason Gore (2005 84 Lumber Classic). Lee Westwood later won in June as a Sponsor Exemption at the St. Jude Classic presented by Smith & Nephew.
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.
World Golf Championships-Accenture Match Play Championship: In his fourth consecutive start at the World Golf Championships-Accenture Match Play Championship, fought his way to the semifinals Sunday morning against Ernie Els. Got off to a hot start, leading for seven of the first nine holes. With a shift of momentum, Els battled back and won three consecutive holes (Nos. 10-12) to gain a 2-up lead. Following an eagle and par on Nos. 13 and 14, he squared up the match. An Els birdie-3 at No. 18 sent the match to extra holes. A birdie-3 at the 19th hole (No. 1) gave him the upset win over Els.
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.
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 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.