Third seed Bouchard, of Canada, played with heavy strapping on her left thigh in New Haven on Wednesday, as she did in her first-round thrashing of Bojana Jovanovski.
But the discomfort seemed to put off Bouchard, who was no match for wildcard Sam Stosur - the Australian posting a 6-2 6-2 victory in one hour 13 minutes.
Bouchard, ranked eighth, has won only one of four matches since her run to the Wimbledon final.
World number 25 Stosur, meanwhile, is finding form at the right time of the year, heading towards the major at Flushing Meadows - which she took out in 2011.
Stosur will meet fellow wildcard Kirsten Flipkens in the quarter-finals, after the Belgian won a three-hour contest over Germany wildcard Andrea Petkovic 4-6 7-6 (9-7) 7-6 (8-6).
Flipkens showed plenty of poise to hold on in the third set tie-break after coughing up a 6-3 lead, eventually sealing the victory on match point number four with an overhead smash.
Danish fourth seed Wozniacki was humbled by Camila Giorgi 6-4 6-2 in one hour 18 minutes.
Giorgi rose to prominence with a win over Wozniacki at the 2013 US Open, and a week out from the New York major, she proved it was no fluke.
The Italian will face Spain's Garbine Muguruza for a spot in the last four, after the latter downed China's Peng Shuai 6-2 3-6 6-3.
Peng had all the momentum after taking the second set, and breaking Muguruza in the first game of the deciding set.
But the big-serving Spaniard showed plenty of resilience, breaking in the fourth and sixth games to take the upper hand and stroll to the finish line.