Novak Djokovic and Naomi Osaka, the world's top-ranked players, are out of Indian Wells, but British No 1 Kyle Edmund is through to the last 16.
Djokovic fell at the hands of Philipp Kohlschreiber 6-4 6-4, while Osaka lost to Belinda Bencic 6-3 6-1.
Edmund booked his spot in the fourth round with a straight-sets 6-3 6-3 win against qualifier Radu Albot and will meet Roger Federer next.
World No 1 Djokovic had owned an 8-1 record against Kohlschreiber before their encounter but failed to find the right notes to push past his opponent on this occasion.
Instead, the victory marked Kohlschreiber's first win over a No. 1 player and he will meet Gael Monfils in the fourth round.
Djokovic and Kohlschreiber resumed their third-round match after it was suspended because of rain a night earlier and the World No 1 congratulated his opponent's ability to adapt to the different conditions.
"I liked my chances more at night against Kohlschreiber, but it wasn't to be last night," said Djokovic.
"Completely different conditions today. I congratulate him for playing tactically really well and getting me out of my comfort zone. He deserved to win."
After demolishing Nicolas Jarry in 52 minutes last time out, Edmund was equally ruthless against Albot.
The 24-year-old, who is currently ranked 23 in the world, won 84 per cent of his first-serve points to triumph in just an hour and 14 minutes.
It put an end to Albot's nine-match winning streak, after the 29-year-old Moldovan claimed the maiden tour title of his career at Delray Beach last month.
The reward for Edmund's clinical work is a duel with Federer for a place in the quarter-finals. Federer defeated his Swiss compatriot Stan Wawrinka 6-3 6-4 to keep his own campaign on track.
In the women's competition, Osaka followed Simona Halep through the exit door after a fourth-round loss at the hands of Bencic.
World No 1 Osaka never found her rhythm as the Swiss player used her precise ground-strokes and pinpoint serving to topple the defending champion 6-3 6-1 in just over an hour.
Bencic has made a habit of upending top-10 players of late, defeating four en route to winning the Dubai Duty Free Tennis Championships last month. Her opponent in the quarter-finals will be Karolina Pliskova.
Elsewhere, Halep lost to Marketa Vondrousova 6-2 3-6 6-2, and Kiki Bertens was beaten by 20th-seeded Garbine Muguruza 5-7 6-1 6-4.
Venus Williams booked a last-eight clash with Angelique Kerber as she recorded a 6-4 6-4 win over Mona Barthel, and was pleased with her performance.
"I haven't played that much, so I wanted to make it count," said Williams, who expects to play about 12 tournaments this year.
"I need to do what I want, and what I want is to play the tournaments I want to play."
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