Novak Djokovic and Maria Sharapova both survived unscathed but the Sony Open lost two other grand slam champions on Friday when Victoria Azarenka and Juan Martin Del Potro exited the Miami tournament.
Azarenka withdrew from her opening match because of an ankle injury she suffered playing at Indian Wells last week.
"I'm very disappointed ... But I have to take my health into consideration," said Azarenka, who won the Australian Open in January but has struggled with injuries since.
"I tried everything I could but couldn't make it. It's an unfortunate part of our job."
Azarenka's withdrawal proved an unexpected bonus for American teenager Lauren Davis, who failed to qualify for the tournament.
She was given a 'lucky loser' pass into the event when Azarenka pulled out then saved three match points in defeating Madison Keys 6-1, 5-7, 7-6.
"I just hoped and I wished and I prayed that I would get in," said Davis. "I was just so happy. I didn't care if I won or lost. I just was so grateful for the opportunity to play."
Former U.S. Open champion Del Potro last week, suffered a surprise 7-6, 6-1 loss to Germany's Tobias Kamke.
The towering Argentine had two set points in the opening set but lost his way just a week after making the men's final at Indian Wells.
"He didn't play obviously his best tennis," said Kamke. "But still I think I did a good job and pretty satisfied with that."
There were no other major casualties amongst the top seeds, with Djokovic and Sharapova both winning in straight sets.
Sharapova romped to a 6-2, 6-0 win over Canada's Eugenie Bouchard while Djokovic, playing in the late night match, cruised to a 6-1, 6-0 victory over Lukas Rosol.
Only Spain's David Ferrer, the men's third seed, had an easier time. He won in a walkover when Dmitry Tursunov pulled out.
Photograph: Clive Brunskill/Getty Images