The big-serving sixth-ranked South African hit 15 aces and won 86 per cent of first serves in en route to the 7-5 6-3 victory.
The Greek teenager - who has surged to No. 27 in the world rankings from No. 168 a year ago - reached his first career semifinal at an ATP World Tour Masters 1000 event.
Tsitsipas reached his first ATP World Tour final earlier this year at a clay-court event Barcelona, losing to Spanish great Rafael Nadal in the championship match.
Upset scenarios were not in the plan of holder Alexander Zverev, who rolled over Russian Daniil Medvedev 6-3, 6-2 in just 52 minutes while never facing a break point.
The favourite was much improved in the second set but still could not shake off Tsitsipas, needing to save two late break points as his opponent closed on victory.
"I'm happy to see Stan playing well again".
Counterprotesters expected to eclipse white supremacists in DC
The rally on Sunday, called Unite the Right II, is scheduled to take over Lafayette Square for two hours in the evening. Extra precautions, including a firearms ban, have been taken to help prevent violence during this year's gathering.
Serbian tennis maestro Novak Djokovic has set his sights on the upcoming edition of Cincinnati Open following his ouster from the Toronto Masters.
Nadal is next scheduled to face Croatian Marin Cilic, who beat Argentina's Diego Schwartzman 6-3, 6-2.
"I knew I was playing pretty good today", he said. I had my chances to come back in the third set when I dropped my serve at 15-40.
Heavy morning rain pushed back the opening matches at the York University campus in the north end of the city by about an hour, holding off the start of an exciting day that featured six Canadian players, including Montreal's Felix Auger-Aliassime on his 18th birthday. Even his win over Serbia's Djokovic was not pulled out of a hat. "I just played not that great". But I think one is good to give away to a top player, but two is, in my opinion, pushing it'.
Anderson topped qualifier Ilya Ivashka of Belarus 7-5, 6-3, and Dimitrov beat American Frances Tiafoe 7-6 (1), 3-6, 7-6 (4).
In the doubles quarterfinals, the top-seeded duo of Austria's Oliver Marach and Croatia's Mate Pavic edged Jean-Julien Rojer of the Netherlands and Romania's Horia Tecau 6-7 (5), 7-5, 10-6.