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.
The Open Championship: Enjoyed his best finish among seven major championship starts, with a T5 at The Open Championship at Royal St. George's. Opened with three par-or-better rounds to enter the final round three strokes behind Darren Clarke. Closed with a 2-over 72 in windy conditions to finish tied with fellow Americans Chad Campbell and Anthony Kim.
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.
In the 2012–13 season, Lowry regained his first team place, playing in the left-back and central defense positions until he missed one game after picking up a yellow card for the fifth time against Bristol City on 2 October 2012. After making his first team return as a left-back, Lowry then provided assist for the winning goal when he set up a goal for Chris Woods, in a 1–0 win against his former club, Leeds United on 18 November 2012. Lowry was then banned for two matches between 19 January 2013 and 25 January 2013 after picking up a yellow card for the tenth time this season. Lowry then He "curled a superb, dipping free-kick" to score from 35 yards (32 m) as Millwall beat Charlton Athletic 2–0 at The Valley on 16 March 2013. Lowry played in all matches in the run up to the Lions' FA Cup semi final against Wigan Athletic at Wembley, though he missed one match in the 4th round against his former club, Aston Villa. In late-April, Lowry was given a three match ban after being booked for the fifteenth time this season. Despite this, Lowry finished the 2012–13 season, making forty-five appearance and scoring once in all competitions.
Lowry did not win on the European Tour from 2016 to 2018 but was joint runner-up in the 2017 DP World Tour Championship, Dubai and runner-up in the 2018 Andalucía Valderrama Masters. In January 2019 he won the Abu Dhabi HSBC Championship by a stroke from Richard Sterne. Lowry led by 3 strokes after three rounds but was two-over-par after 11 holes of his final round and dropped 4 shots behind Sterne. However he finished with 3 birdies in the final 7 holes, while Sterne had two bogeys, giving Lowry the victory.
In June 2015, he became the first SMU Mustang to win the NCAA individual championship, recording a score of 280 (−8) to win by one stroke. In August, he won the U.S. Amateur title, defeating Derek Bard 7 & 6 in the 36-hole final. He became the fifth player to win both the NCAA and U.S. Amateur titles in the same year, joining Jack Nicklaus (1961), Phil Mickelson (1990), Tiger Woods (1996), and Ryan Moore (2004).