And the world number one sent an ominous warning to his rivals for glory in Monaco with a straightforward win on Wednesday.
Pouille lost the ground and he netted an easy forehand in game two to lose his serve for the first time, falling 4-0 behind thanks to another forehand error.
Both men exchanged blows in the first set, but it was Djokovic who jumped to a 5-1 lead in the tie-break. Instead of bringing the set home, Zverev double faulted in the following game to drop serve and Muller delivered another break in game 10 with a drop shot victor to steal the opener 6-4, rattling off 12 of the last 14 points.
Though the Croat had lost their only previous meeting, circumstances could hardly be more different from when the all-conquering Djokovic humbled him 6-2 6-4 in Madrid - just weeks before winning his fourth Grand Slam in a row at the French Open - compared to the injury-hit, confidence struck player that stood opposite the net in Monte-Carlo.
He saved a match point when Rublev served at 5-4, 40-30 but hit a forehand narrowly wide. The 10th match point did the trick with Coric sending a backhand long.
Nadal kicked off his bid for an 11th Monte Carlo title by breezing to a 6-1 6-3 win against world number 58 Bedene.
The Spaniard, who is chasing a record 31st ATP Masters 1000 title, will take on Russian Karen Khachanov in the last 16.
Nadal brought up set point in the opener with a trademark, curling forehand up the line, before sealing the set with a drop shot.
"I mean, I could have won the match earlier definitely, but it was great to deal with these kind of emotions again", said Djokovic.
Two breaks of serve were enough to wrap up the opening set and, while Bedene put up more of a fight in the second, Nadal simply had too much for his Slovenian opponent.
Japan's Kei Nishikori continued his comeback from injury with an impressive 7-5, 6-2 win over Russian Daniil Medvedev.
The former world No 4, who has struggled over the past year with a right wrist injury, followed up his first-round victory against Tomas Berdych with a solid display on centre court.
The 12-time Grand Slam victor, who ended a three-match losing streak with victory over Dusan Lajovic in his opening match earlier this week, came through against the talented 21-year-old Coric thanks to a a 7-6 (7-2) 7-5 victory.
Roberto Bautista-Agut, meanwhile, defeated Feliciano Lopez to set up an intriguing third-round tie with David Goffin, while Jan-Lennard Struff took out Fabio Fognini to book a clash with Alexander Zverev.