World number one Iga Swiatek saw her 37-match winning streak ended as France's Alize Cornet caused one of the biggest upsets so far at Wimbledon.
Cornet, 32, kept her composure to streak towards a famous victory.
Coco Gauff was also knocked out as fellow American Amanda Anisimova fought back from a set down to reach the fourth round for the first time.
The 20-year-old, making her Centre Court debut, took control in the final two sets as she wrapped up an impressive 6-7 (4-7) 6-2 6-1 win.
Anisimova has reached the last 16 of all three Grand Slams this year.