American Sloane Stephens snatched her second major scalp of the season as she toppled former champion Maria Sharapova in the second round at Cincinnati on Tuesday.
Stephens rallied to beat the world number three from Russia 2-6, 7-6 (7/5), 6-3, bringing Sharapova's injury return to an abrupt end in this combined WTA and ATP Masters hardcourt tournament.
While Sharapova -- who enjoyed a first-round bye -- was struggling with her game, Roger Federer made a smoother comeback after dealing with back pain in recent weeks.
The five-time champion who is defending the title and needs as many matches as possible before the August 26 start of the US Open, won his seventh career match against German friend Philipp Kohlschreiber 6-3, 7-6 (9/7).
The fifth-ranked Swiss felt in his element as he played the tournament for the 13th time, improving his record to 31-10 this season.
"I think it was a match where I had to sort of just fight to come through and hope to get over the finish line," Federer said. "I was playing really well at times, and then sometimes it was maybe a bit up and down.
"Assessing the performance overall, I'm very happy. It's good to be back and playing pain free. I don't know, my mind's good. I was in a good place while I was playing, so it felt nice to win at the end."
Spanish third seed David Ferrer joined Federer in the third round with a 7-6 (7/5), 3-6, 6-4 victory over American Ryan Harrison.
Montreal finalist Milos Raonic struggled in the opening set against Jack Sock, but found his rhythm for a 3-6, 6-4, 6-3 win and a date on Wednesday with Janko Tipsarevic.
Sharapova was making her return to tennis seven weeks after her last match, a shock second-round Wimbledon defeat.
Since then she had sacked her coach and begun working with Jimmy Connors, all while she battled to get over a hip injury.
The four-time Grand Slam champion was bedevilled by more than 60 unforced errors.
A nervous Stephens, who stunned Serena Williams at the Australian Open, double-faulted on two match points before finally claiming the victory on a third.
"I started the match off pretty well, but when you put yourself in a really good position you can't let it go. That's what I did tonight," Sharapova said.
"I didn't continue what I was doing well for the first set and a half, and that hurt me.
"I stopped being patient, I started making a lot more errors, especially off the first ball. Just errors that I shouldn't make."
Second seed Victoria Azarenka reached the third round, beating American Vania King 6-1, 7-6 (8/6).
Azarenka was playing for the first time since losing the Carlsbad final to Samantha Stosur, then withdrawing injured from Toronto.
In the first round, former number one Caroline Wozniacki defeated China's Peng Shuai 6-1, 6-1 while Jelena Jankovic, the number 14, spoiled the return to action of Wimbledon finalist Sabine Lisicki 7-6 (7/5), 5-7, 6-2.
Germans Mona Barthel and Andrea Petkovic both won, with Barthel defeating Lucie Safarova 6-3, 6-4 and Petkovic stopping Daniela Hantuchova 2-6, 6-4, 6-1.
But two other Germans lost as Magdalena Rybarikova, the Washington champion, beat Julia Goerges 6-2, 4-6, 6-4 and Ekaterina Makarova defeated Annika Beck 6-3, 6-2.
In other men's results, Feliciano Lopez opened with a 6-4, 7-6 (7/4) upset of Japanese 10th seed Kei Nishikori, while German 11th seed Tommy Haas made up for an early exit a week ago in Canada by reaching the second round with a 6-4, 6-4 win over South African Kevin Anderson.
Russian veteran Nikolay Davydenko stopped Frenchman Benoit Paire 7-6 (10/8), 6-3 and Spaniard Tommy Robredo beat Brazil's Thomaz Bellucci 6-7 (6/8), 7-6 (9/7), 6-2.
Canadian Vasek Pospisil, who has jumped to 40th in the world after his Montreal semi-final appearance, advanced to the second round when France's 15th seed Gilles Simon retired trailing 6-2, 1-1 with a hip injury.