Qualified for his sixth U.S. Open by sharing medalist honors at the Columbus, Ohio, sectional with Sungjae Im, posting 9-under 135 at The Lakes Golf & Country Club and Brookside Golf & Country Club. Lowry was in contention to win his first major in the 2016 U.S. Open at Oakmont until three consecutive bogeys from No. 14 pushed him to a share of second place, three strokes behind winner Dustin Johnson. The Irishman broke through for his first victory on U.S. soil by two strokes over Bubba Watson in the 2015 WGC-Bridgestone Invitational at Firestone Country Club. He owns two other wins on the European Tour, including the 2009 Irish Open as an amateur. Other notable victories include the 2012 Portugal Masters and the 2007 Irish Amateur Closed Championship. Lowry represented Ireland in the 2008 World Amateur Team Championship.
| Year | Site | Scores | To Par | Finish |
| 2018 | Shinnecock Hills Golf Clulb | 75-79 | +14 | MC |
| 2017 | Erin Hills | 71-74-73-73--291 | +3 | T-46 |
| 2016 | Oakmont Country Club | 68-70-65-76--279 | -1 | T-2 |
| 2015 | Chambers Bay | 69-70-70-71--280 | E | T-9 |
| 2014 | Pinehurst Resort & C.C. (Course No. 2) | 73-73 | +6 | MC |
| 2011 | Congressional Country Club | 72-76 | +6 | MC |