Novak recorded a 6-4, 7-5 victory over Feliciano Lopez in one hour and 33 minutes on Thursday.
Nole will next play against no.10 seed David Goffin, who recorded a 7-6, 4-6, 6-3 win over sixth seed Dominic Thiem earlier in the day.
Djokovic earned his 300th ATP World Tour Masters 1000 victory, beating no.31 seed Juan Martin del Potro 7-5, 4-6, 6-1.
Novak reached the last eight defeating Canada's Vasek Pospisil 6-4, 6-4. He next faces German qualifier Mischa Zverev (ATP #110).
No.1 seed defeated world no.66 Aljaz Bedene 6-2, 6-3, 6-3 to reach the last 16 of Roland Garros.
The top seed defeated world no.37 Thomaz Bellucci 0-6, 6-3, 6-2 to set up a quarter-final showdown with Rafael Nadal (ESP, 5).