Ashleigh Barty and Sloane Stephens bowed out of the Rogers Cup on a day of upsets in Toronto on Tuesday.
World number one Barty and last year's runner-up Stephens were two of five seeds to fall at the WTA Premier tournament in Canada.
While that pair departed in the second round, Madison Keys, Aryna Sabalenka and Anastasija Sevastova were first-round losers.
BARTY, STEPHENS BOW OUT
In action for the first time since Wimbledon, Barty suffered a shock 6-7 (5-7) 6-3 6-4 loss to American Sofia Kenin.
The Australian is now at risk of losing her top ranking, with Naomi Osaka and Karolina Pliskova having the chance to return to number one.
The only way Barty will remain number one is if Osaka loses her opening match and Pliskova fails to reach the semi-finals.
Runner-up last year, Stephens went down to qualifier Marie Bouzkova 6-2 7-5 for her third straight loss.
SEEDS SLIP UP
Keys almost got through her opener, but eventually lost to Donna Vekic 3-6 7-6 (7-5) 7-6 (7-5) after squandering three match points.
The American, runner-up in 2016, served for the match at 5-4 in the second set, only to give up a 40-0 lead before bowing out.
Sabalenka was also edged, going down to Anastasia Pavlyuchenkova 3-6 6-3 7-5.
Sevastova, the 10th seed, was beaten by China's Zhang Shuai 7-6 (7-5) 6-2, with Kiki Bertens the only seed to progress.
Bertens thrashed qualifier Francesca Di Lorenzo 6-2 6-1 in just over an hour.
AZARENKA POWERS THROUGH, VENUS DEPARTS
Victoria Azarenka booked her spot in the second round thanks to a 6-2 6-2 victory over Camila Giorgi.
The 2014 runner-up Venus Williams, meanwhile, was well beaten by Carla Suarez Navarro 6-4 6-2.
In an all-Canadian clash, Bianca Andreescu got the better of wildcard Eugenie Bouchard 4-6 6-1 6-4.