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).
The world no.1 got pass into the US Open fourth round as Mikhail Youzhny retired injured at 4-2 for the defending champion.
Three-time former champion beat world no.129 Radek Stepanek 6-2, 6-4 to advance into the last eight in Toronto.
The American ended Novak’s remarkable Grand Slam winning run, downing the top seed and defending champion 7-6 (6), 6-1, 3-6, 7-6 (5).
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).
The world no.1 clinched his spot in the 2016 Mutua Madrid Open quarter-finals with a 6-2, 6-1 victory over Roberto Bautista Agut.
Nole earned a place in the fourth round of the 2016 Miami Masters with a 6-4, 6-1 win over no.33 seed Joao Sousa on Sunday.