Tsitsipas, who turns 20 on Sunday, beat the 13-time Grand Slam champion 6-3 6-7 (5-7) 6-3 in two hours 18 minutes.

The world number 27 is through to the first ATP World Tour Masters 1000 quarter-final of his career.

World number one Rafael Nadal is also through to the last eight.

The Spaniard beat Switzerland's Stan Wawrinka 7-5 7-6 and will play Croatia's world number seven Marin Cilic in the next round.

Second seed Alexander Zverev is next up for Tsitsipas, after the German beat Russia's Daniil Medvedev 6-3 6-2.

Kevin Anderson will play Bulgarian Grigor Dimitrov in the quarter-finals.

South Africa's Anderson, who Djokovic beat in this year's Wimbledon final, saw off Belarus' Ilya Ivashka 7-5 6-3.

Dimitrov beat Frances Tiafoe of the United States 7-6 (7-1) 3-6 7-6 (7-4).

Completing the quarter-final line-up is the match between Russia's Karen Khachanov and Robin Haase of the Netherlands.