Four-time major champion McIlroy holed out an approach shot for an eagle en route to a 4-under 67.
After producing only one birdie on his opening nine holes — having starting his round on the back nine — McIlroy shot up the leaderboard when he landed his second shot from 115 yards on the par-4 third a few feet from the hole. The ball then rolled in and McIlroy lifted his arms in delight as he watched from afar back up the fairway.
Fitzpatrick was one stroke ahead at 5-under through 15 holes when play was suspended because of darkness.
McIlroy went 5-under over his final seven holes.
The start of play was delayed for an hour because of lightning and conditions remained blustery throughout the day.
On the par-5 626-yard 18th, McIlroy drove his tee shot into high grass and had to chip out into the fairway before eventually sinking a 20-foot putt to save par.
McIlroy has finished first and second respectively in his previous two tournaments, the Tour Championship in Atlanta and the BMW PGA Championship in Wentworth, England, last week.
From Sept. 29 to Oct. 1, 2023, Marco Simone will become the third venue in continental Europe to host the Ryder Cup after Valderrama in Spain (1997) and Le Golf National in France (2018).