After starting with four pars, Lowry – who is without an individual victory since September 2022 – carded back-to-back birdies at the fifth and sixth holes.
The former Open champion vaulted into a share of the lead with a run of five straight birdies from the par-four 11th before picking up a shot at the last to edge ahead of Nakajima.
“It’s not that hard when you hit it in play out there, but you start missing fairways it becomes quite tricky, so I’m happy with that,” said Lowry.
He added: “You need to shape it around the course, hit it in position off the tee and it’s all about your iron play. That’s one of my strengths and I took advantage of that today and managed to roll a few putts in on the back nine, which was nice.”
Lowry added there was a “little bit” of Ryder Cup chat with playing partners Fleetwood and Donald.
“We could hear the horns from the road, it was not as off-putting as the Bethpage [Black] crowd,” he said with a smile, referring to the hostile New York fans at last month’s Ryder Cup.
Fleetwood mixed four birdies, an eagle and two bogeys to sit four shots back.
Donald, who is playing his first tournament since his second Ryder Cup success as captain, carded five birdies and a bogey to match fellow Englishman Fleetwood and 2023 Open champion Brian Harman.
Playing with McIlroy, US Ryder Cup player Ben Griffin opened with a 68 while McIlroy’s European team-mate Viktor Hovland signed for a 71.
