Bouchard lost 6-2, 6-2 to Australian Samantha Stosur. The Canadian, ranked No. 8 in the world, played with her left thigh wrapped after straining her hamstring in practice this week. The injury left her visibly struggling with her mobility throughout the match.
"It's obviously not ideal; I've had to cut back a little bit on practice time, but I should be good to go pretty soon," she said.
Bouchard said her personal trainer will join her in New York and said she does not expect the injury to have much of an impact on her performance at next week's U.S. Open.
Stosur, ranked No. 25 in the world, dominated the match, winning almost 70 per cent of the points on her serve, while breaking Bouchard's serve twice in each set.
"My serve is a weapon, and sometimes it doesn't act like that, so it's important for me to really use that part of my game to my best advantage," said Stosur, who will play in her first quarterfinal since January.
Wozniacki, the fourth seed, was beaten 6-4, 6-2 by Camila Giorgi of Italy.
Giorgi, who also beat Wozniacki in last year's U.S. Open, faced just two break points. Her first serves reached 117 mph and her second serves hovered around 107 mph.
She consistently hit ground strokes at Wozniacki's feet, preventing her from moving laterally.
The 37th-ranked Giorgi broke Wozniacki's serve in the first game of the match and twice in the second set.
"I think today the serve was the key and really consistent," she said.
It was the earliest exit at this tournament for Wozniacki, who has appeared in New Haven seven times. She won in each of her first four trips and lost in the semifinals in 2012 and 2013.
Wozniacki is ranked No. 11 and was seeded fourth this year. But she also has been training to run the New York Marathon while keeping up a full tennis schedule. She said the cross-training has not been a problem, but acknowledged being tired on Wednesday.
"I haven't had a day off basically since I came to Montreal, so I've been playing almost every day," she said. "The tank just wasn't full today and when you play a player like that you just don't get by with not moving 100 per cent."
Giorgi will play Garbine Muguruza in the quarterfinals. Muguruza, ranked 26th in the world, needed three sets to dispatch qualifier Peng Shuai of China 6-2, 3-6, 6-3.
Muguruza dropped the first two games of the final set, but won the next five games en route to the victory.
"I was nervous because I didn't know what to do at that point," Muguruza said. "But I just said to myself, 'Just continue, because she's also going to get nervous or she's going to miss and not continue like this."
Kirsten Flipkens of Belgium came from behind to beat Andrea Petkovic of Germany 4-6, 7-6 (4), 7-6 (6) in a match that lasted 3 hours, 11 minutes. Petkovic served for the match twice in the second set at 5-4 and again at 6-5, but could not close out Flipkins.
Flipkins also had a tough time ending the match. She led 6-3 in the final tiebreaker before winning on her fifth match point.
"I had to fight for it," Flipkins said. "It was one of the best battles of my career."
Just one seeded player, second-seed Petra Kvitova, has advanced to the quarterfinals of the tournament. She won her second-round match on Tuesday and faces Barbora Zahlavova Strycova of the Czech Republic on Thursday.
The other quarterfinal has American Alison Riske against Magdalena Rybarikova of Slovakia.