Petra Kvitova, ranked No. 2 and playing in her first event since winning her second Wimbledon title, fell 6-4 1-6 6-2 to Russia's Ekaterina Makarova while fourth seed Maria Sharapova was beaten 6-2 4-6 6-2 by Spain's Carla Suarez Navarro.
German sixth seed Kerber and seventh seed Jelena Jankovic of Serbia were also sent packing, leaving just two of the top eight seeds - Serena Williams and third seed Agnieszka Radwanska of Poland - in the quarter-finals.
Playing in Montreal for the first time in 14 years, world number one Williams has looked at ease on the hardcourts after winning the tournament in Toronto last year.
While not as ruthless as in her 6-2 6-0 demolition of former-US Open champion Sam Stosur in her opening match, the American still delivered on the big points when it mattered against her 15th-seeded Czech opponent.
"I really needed to serve well today because she was just hitting unreturnable serves for me," said Williams. "We didn't really have too many long rallies.
"We both were just hitting lots of service winners or aces. So it was kind of hard to get in a good rhythm."
Williams will now face Denmark's former world number one Caroline Wozniacki, who brought American qualifier Shelby Rogers' fairytale run to a shuddering 6-1 6-0 end, in the quarter-finals.
"Obviously Serena has all the experience. She has a big serve. She takes the ball early," said Wozniacki.
"I would need to try and make her move, try and open up the points, serve well myself.
"Serena is obviously a great champion. She's an unbelievable player. You can see that with how many grand slams she's won, how many tournaments she's won.
"It's never a surprise whenever she's doing well. She's ruling the court."
Venus Williams joined her sister in the quarter-finals with a 6-3 3-6 6-4 win over Kerber.
It was the second time in four days that Kerber fell to a Williams, as Serena beat the German in the Stanford final in California on Sunday.
"So many matches I've been on the short end of the stick. It felt good this time to pull one out," Venus said after her second career win in five head-to-head matches with Kerber.
American Coco Vandeweghe beat Jankovic 7-6(8) 2-6 7-5. Vandeweghe won three fewer points but still prevailed.
Rogers Cup results
3-Agnieszka Radwanska (Poland) beat Sabine Lisicki (Germany) 6-1 3-6 6-3
8-Victoria Azarenka (Belarus) beat Heather Watson (Britain) 6-2 6-4
Venus Williams (U.S.) beat 6-Angelique Kerber (Germany) 6-3 3-6 6-4
Coco Vandeweghe (U.S.) beat 7-Jelena Jankovic (Serbia) 7-6(8) 2-6 7-5
1-Serena Williams (U.S.) beat 15-Lucie Safarova (Czech Republic) 7-5 6-4
Ekaterina Makarova (Russia) beat 2-Petra Kvitova (Czech Republic) 6-4 1-6 6-2
11-Caroline Wozniacki (Denmark) beat Shelby Rogers (U.S.) 6-1 6-0
- Sports & Recreation
- Serena Williams
- Maria Sharapova
- Venus Williams
- Ekaterina Makarova
- Jelena Jankovic
- Petra Kvitova
- Caroline Wozniacki
- Agnieszka Radwanska
- Carla Suarez Navarro