The Serb, who is chasing a record-extending 25th Grand Slam title, sealed his 370th match victory at the majors that broke a tie with retired Swiss great Roger Federer but his title rivals will be smelling blood after another up-and-down display.
When the dust settled on his second five-setter in less than 48 hours at Roland Garros, Djokovic celebrated reaching his 59th major quarter-final - the most by any men's player - to eclipse his long-time rival Federer again.
An 11th five-set win at Roland Garros also tied him with Gael Monfils and Stan Wawrinka in the Open Era list.
"Again a big, big, big thank you because once again like the last match. The win is your win," an exhausted Djokovic told the Court Philippe Chatrier crowd in fluent French.
The veteran showed no early signs of fatigue from his marathon third-round win over Lorenzo Musetti, a four-and-a-half hour epic that ended in the early hours of Sunday morning, as he blitzed claycourt specialist Cerundolo in the opening set.
He sustained a right knee issue early in the next and needed treatment on court before saving four break points to draw level at 3-3 with a backhand bullet but allowed his opponent a way back in by surrendering his serve in the 12th game.
Cerundolo grabbed another break early in the next set to go 3-0 up and comfortably got ahead in the clash as alarm bells began to ring for Djokovic in a second straight match at the claycourt Grand Slam he has won three times.
The finish line seemed to appear in sight for Cerundolo when he raced up 4-2 in the next set, but he squandered the advantage as Djokovic sent down two big serves and produced a spectacular drop en route to holding for 6-5 before levelling the contest.
Having dropped serve after a fast start in the deciding set, Djokovic took a nasty tumble during a point and ranted about the state of the Court Philippe Chatrier surface.
He dusted himself off and the smile returned shortly after as he executed a sensational drop volley while doing the splits at 3-3 and celebrated the point by lying on the court with his arms outstretched in a superhero pose.
With the crowd firmly behind him, Djokovic closed out a superb victory and paid tribute to fans on the main showcourt at around 21:00 local time.
The world number one will next face Casper Ruud, who battled past Taylor Fritz 7-6, 3-6, 6-4, 6-2 later in the day.