The World Number Four made five birdies and an eagle on Friday afternoon to lead by one over Denmark's Jeff Winther.
"I played really solid again," said Fitzpatrick, who is making his first appearance at the event since 2018.
"Felt comfortable with my game. Just the last few holes were a bit of a grind. But, yeah, happy to be in the clubhouse."
The start of the second round was delayed by fog on Friday morning but, once play got under way, Winther quickly became the man to catch.
With first round leader Michael Kim among the later starters, the Dane fired a bogey-free 64 of his own to reach 12 under and set the early target.
Fitzpatrick, playing in the afternoon, made four birdies on the front nine to move quickly into contention. After four straight pars from the turn, he then joined Winther at the summit with an eagle at the par-five 14th before holing a 27-footer at the 16th to take the outright lead.
He parred the 17th but slipped while playing his approach to the last, sending the ball long and left of the water-surrounded green and leaving himself a difficult up-and-down.
Fitzpatrick responded by playing his next shot to four feet before converting the par putt to sign for a flawless 64 and a 36-hole total of 13 under.
"Yeah, the shot itself, we were wondering whether to go for it. I was kind of happy to go for it. Took the extra club just to make sure.
"And then as I took my backswing, I felt my right foot slip. So I kind of obviously was then in search for the ball, I kind of throw my right arm and managed to sort of make contact, it's just gone a long way and a long way left.
"But, yeah, obviously nice to be in the fairway, be able to have some control on the ball and hit one in close."
Defending champion Michael Kim, who claimed his maiden DP World Tour crown at this event 12 months ago at Golf de Saint-Nom-La-Breteche as Le Golf National underwent extensive renovations, sits a shot further back.
Fellow American Ryan Gerard and Frenchman Tom Vaillant currently share fourth on ten under, with Angel Hidalgo, Marcel Siem, Thriston Lawrence and Gregorio De Leo in a share of sixth place at nine under.