Fourth seed Elina Svitolina suffered a shock defeat on the opening day in Birmingham as she lost 6-3 3-6 6-4 to Russia’s Margarita Gasparyan.
The 24-year-old broke the Ukrainian’s serve in the opening game on her way to taking the first set.
Svitolina, also 24, who won the WTA Finals event in 2018, secured an early break in the second set to level it.
But Gasparyan gained a 4-1 lead in the deciding set and held on for the victory.
The Russian, who is ranked 62nd in the world and has recently recovered from a career-threatening knee injury, said: “It was a tough time and I didn’t know if I could play tennis any more but now I’m here in a big tournament so this is something special for me.”
Gasparyan will play either compatriot Ekaterina Alexandrova or Petra Martic of Croatia in the last 16.
British players Heather Watson and Johanna Konta are among those in action later on Monday in the Nature Valley Classic.
There will be a live text page on the BBC Sport website as Konta, who reached the semi-finals of the French Open earlier this month, takes on world number 20 Anett Kontaveit of Estonia.
- Live scores, schedule and results
- Alerts: Get tennis news sent to your phone
The competition is being held at the Edgbaston Priory Club and also includes world number one Naomi Osaka, French Open champion Ashleigh Barty and Karolina Pliskova, ranked third in the world.
In the doubles competition, 22-year-old Briton Harriet Dart partners seven-time Grand Slam singles champion Venus Williams and they face the pairing of Nadiia Kichenok of Ukraine and American Abigail Spears.