Trey Mullinax, Daniel Berger, Luke List, Ryan Moore and Ryan Palmer were tied for second.
Top-ranked Dustin Johnson, coming off a second-place tie at Masters last week, rallied with two birdies in his final seven holes for a 68, leaving him three shot back.
Lowry had not broken 70 in a stroke-play event since a 67 in the third round at the AT&T Pebble Beach Pro Am in early February on his way to missing the cut. The Irishman missed three more cuts in the past five weeks, including going 78-73 to end his Masters after two rounds.
Things changed for Lowry at Harbour Town Golf Links, where he birdied three of his first six holes. He made three more birdies on his back nine.
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