World number one Aryna Sabalenka and Jessica Pegula were both upset in fourth-round matches on Saturday in Toronto.
Four-time Grand Slam winner Sabalenka suffered a blow to her preparations for a tilt at a third consecutive US Open title, beaten 7-6(3), 4-6, 6-4 by Russian 16th seed Ekaterina Alexandrova.
"I wasn't trying to think about the score or anything like beating number one," said Alexandrova after ousting the Belarusian in 2hr 29min.
"I was just trying to do my best.
"I just tried to play every single point as if it was the last one because with her, you don't get a lot of chances during the match," Alexandrova said.
"I had a lot today, but I couldn't realise some of them. I'm super happy that I could win because after the second set, I thought (winning) was already past me."
Alexandrova moves on to a quarter-final against Ukraine's Elina Svitolina, who dispatched American Amanda Anisimova 6-2, 6-4 in 78 minutes.