Defending champion Garbine Muguruza, playing for the first time since losing in the second round of her Wimbledon title defence, fell 2-6, 6-4, 6-4 to Lesia Tsurenko
World No 1 Simona Halep under pressure as rain halts play in Cincinnati
The women's draw took a beating on Wednesday in Cincinnati, where world No 1 Simona Halep was still battling when rain halted play.
The top-seeded Romanian stood 4-6, 6-3, 3-3 against Australian qualifier Ajla Tomljanovic when storms rolled in to bring the night session to an end on a day that had already seen one three-hour rain delay.
Halep had regained some momentum after falling two breaks down in the third set, with both women taking medical timeouts.
Halep was just one of the top women to run into trouble in the combined WTA and ATP Masters hardcourt tournament - the last major tuneup for the US Open.
Defending champion Garbine Muguruza, playing for the first time since losing in the second round of her Wimbledon title defence, fell 2-6, 6-4, 6-4 to Lesia Tsurenko.
"It was a very ugly match, but I'm happy that I fought, even if the level wasn't very high," said Muguruza, who got a late start to her buildup to the US Open because of an arm injury.
"At the end she managed to come back in the third set and play better and found a way to win the match," added Muguruza, who was at least pleased to report that she played without any pain in her arm.
Second seed Caroline Wozniacki, however, retired with a left knee injury after surrendering the first set 6-4 to Kiki Bertens.
The Dane also lost her opening match a week ago in Montreal, following a second-round defeat at Wimbledon.
Wimbledon champion Angelique Kerber, the fourth seed, claimed her 40th win of the season, but she had to recover from a set down and needed two chances to serve for a 4-6, 7-5, 6-4 victory over Russian Anastasia Pavlyuchenkova.
"This was really a match where I was fighting after the first set to coming back," Kerber said. "It was an important match to get my rhythm, feel the ball, especially now after few weeks off."
US Open champion Sloane Stephens bucked the upset trend, winning easily into the third round 6-3, 6-2 over German qualifier Tatjana Maria.
Aryna Sabalenka of Belarus continued her successful tournament debut, beating ninth seed Karolina Pliskova 2-6, 6-3, 7-5. Australian 16th seed Ashleigh Barty defeated Estonian Kaia Kanepi 7-5, 6-3.
Ailing Djokovic advances
In the men's draw Novak Djokovic battled stomach issues to beat Adrian Mannarino and reach the third round.
The Wimbledon champion called for the doctor during the second set but put aside his discomfort to progress 4-6, 6-2, 6-1 over the Frenchman before rain halted afternoon play for nearly three hours.
"I wasn't feeling well, I didn't have a great night and wasn't feeling that well for the first set and a half," said Djokovic, who has won every Masters 1000 title except Cincinnati.
"I made it through, and with the help of the doctor and God ... I'm just, you know, happy that I managed to overcome the challenge."
Fifth seed Grigor Dimitrov launched his title defence with a 7-6, 7-5 win over Mischa Zverev, the Bulgarian belting 33 winners in a match that started late.
Marin Cilic, the 2016 men's champion, beat Romanian Marius Copil 6-7, 6-4, 6-4, but third-seeded Alexander Zverev, younger brother of Mischa, was upset 5-7, 6-4, 7-5 by Dutch veteran Robin Haase.
Wimbledon finalist Kevin Anderson beat Jeremy Chardy 7-6, 6-2 while Canadian Milos Raonic advanced over Malek Jaziri of Tunisia 6-3, 7-5.
Three-time grand slam winner Stan Wawrinka continued his return after knee surgery a year ago, beating Kei Nishikori 6-4, 6-4.
Nick Kyrgios shook off a dismal second set to beat Croatian Borna Coric 7-6, 0-6, 6-3.
The Australian, who petulantly smacked a ball into the stands as he unravelled in the second set, pulled himself together to set up a meeting with either South Korean Chung Hyeon or Argentinals Juan Martin del Potro, whose scheduled match never got underway.