Agnieszka Radwanska, the top seed, and Belinda Bencic, the youngest player in the top world's top ten, both fell at the first hurdle on a day of shocks and rainstorms at the Aegon Classic.
Radwanska, a former Wimbledon runner-up, had intended to use the grass court event as a springboard for another assault on the oldest Grand Slam title, but was halted 7-5,4-6, 6-3 by CoCo Vandewegh, a hard-hitting American ranked outside the top 30.
Vandewegh had never come close to winning a set against Radwanska's consistently skilful ground strokes in four previous meetings, but used her strength and power to good effect.
Even after the Pole intelligently played her way back to parity, Vandewegh maintained a fierce flat attack and managed to break serve three times in the final set.
"Last week helped me get out of tricky situations because I had done it before," said Vendewegh, referring to her capture of the den Bosch title on grass last week.
"I don't think I played so bad today - she was just really good," said Radwanska, disappointed to have had little practice on grass because of the bad weather. This was her first tournament on this surface this year.
Earlier Bencic, arguably the world's most promising player, suffered another injury just ten days after a lengthy spell on the side-lines with a bad back.
The 19-year-old Swiss player's movement had been painful and ponderous before she quit half way through the second set during her first round match against Irina-Camelai Begu.
Bencic's retirement gave the world number 26 from Romania a victory by 6-4, 4-3 retired, though there was hardly a moment when Bencic had been mobile enough to win the match.
She took a tumble on the damp lush grass in the first game, and as early as the fifth game she was seeking help from the trainer. The injury was later described as a thigh strain. "I continued playing more than I should have," Bencic admitted.