Djokovic, who lost to the Greek player three weeks ago in the Shanghai quarterfinals, did not concede a break point. It could have been an even quicker victory considering he led the first set 5-0, 40-0, but Tsitsipas saved three set points and held serve.
The four-time champion broke Tsitsipas in the third game of the second set, then held and broke to love for 4-1. Tsitsipas, who dropped his serve four times, appeared to hurt his left ankle when retrieving a shot near the baseline in the second set.
Serving for the match, Djokovic clinched it on his first match point when Tsitsipas whipped a forehand long following a short rally.
Djokovic, last year's runner-up, is bidding for the year-ending No. 1 ranking. He next plays U.S. Open semifinalist Grigor Dimitrov, and leads the unseeded Bulgarian 8-1 in their career meetings with the only defeat coming on outdoor clay six years ago.
Dimitrov reached his second semifinal this season by beating Cristian Garin 6-2, 7-5, dropping his serve twice and breaking the Chilean's five times.
Later Friday, Nadal faced 2008 champion Jo-Wilfried Tsonga, and Denis Shapovalov played Gael Monfils, who will secure a place in the season-ending ATP Finals in London if he wins.
Nadal is guaranteed to finish the year as No. 1 if he wins the Paris Masters for the first time.