Nadal reached the last eight with a 6-1 6-1 dismissal of rising star Alexander Zverev while Djokovic laboured past Pablo Carreno Busta..
Murray's departure was the biggest surprise. The 29-year-old Briton was 4-0 up in the final set against the 15th seeded Spaniard Albert Ramos-Vinolas
"I'm disappointed to lose from the position that I was in," said Murray, who was making his first appearance on the circuit since a second round loss to Vasek Pospisil at Indian Wells on 12 March and then struggling with an elbow injury that forced to him to skip the Miami Masters the same month.
"If you look at the scoreline, it was 7-5 in the third. One week ago I would have been okay with that. But afer being 4-0 up in the third, I haven't lost many matches like that in my career.
"I'm disappointed. I feel like I had enough chances to win. I was close, I think. My elbow felt pretty good. I served much better and that's only going to get better. So hopefully I keep going in the right direction."
Wawrinka lost in straight sets to Pablo Cuevas of Uruguay.
Of the big guns, Nadal - who is seeking a 10th title in Monte Carlo - proved the most potent. Djokovic was gutsy in his three set win over Carreno Busta.
"I played well. I played more aggressive, I played with a very high intensity from the beginning," Nadal said. "I'm playing much better with my forehand. I maintained that kind of level for all the match, I think that was the key."
Nadal will take on Diego Schwartzmann for a place in the semis while Djokovic will face the Belgian David Goffin.