Top seed Agnieszka Radwanska was beaten by Coco Vandeweghe at the Aegon Classic on Wednesday, while Belinda Bencic withdrew injured on another rain-affected day.
Radwanska, runner-up at Wimbledon in 2012, lost 7-5 4-6 6-3 as Vandeweghe's powerful ground strokes proved too much for the Polish player to cope with.
Vandeweghe, who won the Den Bosch title last week, continued her good form despite having never taken a set off Radwanska in their four previous meetings.
"The rain delays didn't help because you have to keep your mind on the match, which isn't always easy," Vandeweghe said.
"I tried to keep myself quiet and I thought if I could stick with my game plan I could do it."
Up next for Vandeweghe in the Birmingham event is American Christina McHale, who beat Czech Republic qualifier Katerina Siniakova 5-7 6-4 6-3.
The Aegon Classic's fourth seed, Belinda Bencic, pulled out after suffering a thigh strain during her first-round match against Irina-Camelia Begu.
Bencic is the youngest player in the top world's top 10, but the 19-year-old withdrew with the score standing at 6-4 4-3 to her Romanian opponent.
Sixth seed Carla Suarez Navarro set up a second-round tie against Andrea Petkovic by beating Elina Svitolina 7-5 6-4 7-5 in an epic match that took over two-and-a-half hours to complete.
Daria Gavrilova and Tamira Paszek moved into the second round by beating British players Naomi Broady and Tara Moore respectively.
Johanna Konta was due to face Misaki Doi but rain in Birmingham meant the match was delayed until Thursday, while Caroline Wozniacki's match against Belgium's Yanina Wickmayer was also postponed due to the weather, with the Danish player 3-2 up in the first set.