The Englishman has shown no side effects of the short turnaround and fired an eight-under-par 64 at Kingsbarns in the second round to move to 13-under overall.
Fitzpatrick, who won one point from three matches as Europe regained the Ryder Cup from the USA, carded nine birdies against a solitary bogey.
He is targeting his first European Tour victory since lifting his maiden major title at the US Open last year.
Fitzpatrick did win the RBC Heritage tournament on the PGA Tour six months ago.
Spaniard Nacho Elvira and home hope Grant Forrest are tied for second on 12-under, with English pair Matthew Southgate and Marcus Armitage two shots further adrift.
Each player plays one round on the Old Course at St Andrews, Carnoustie and Kingsbarns across the first three days before a 54-hole cut and Sunday's final round at St Andrews.
Fitzpatrick fired a five-under 67 in his first round at Carnoustie on Thursday.
His Ryder Cup teammates in the field, Robert MacIntyre and Tommy Fleetwood, are battling to make the cut on three-under and two-under respectively.
