PHOTOS: The top shots from Wimbledon
Serena, a four-time winner at the All England Club, saved four match points before the ninth-seeded Frenchwoman closed out the contest by hitting a service winner into the corner. Bartoli made the Wimbledon final in 2007, losing to Serena's older sister Venus.
It was the first time Bartoli has beaten the American after straight-set defeats in their previous two matches.
Monday's schedule featured the busiest day in Grand Slam tennis — all 16 men's and women's fourth-round matches.
Top-seeded Caroline Wozniacki, defending champion Serena Williams and five-time champion Venus Williams were all eliminated in the fourth round at Wimbledon on Monday.
Venus Williams' attempt to win a sixth Wimbledon title ended with a 6-2, 6-3 loss to Tsvetana Pironkova of Bulgaria.
The 23-year-old Pironkova beat Williams at Wimbledon last year by the same score to reach her first Grand Slam semifinal. It is the first time since 2006 that neither Williams sister has reached the Wimbledon quarterfinals.
For Wozniacki, Monday's loss extends her streak of never reaching the quarterfinals at Wimbledon. Earlier Monday, fourth-seeded Victoria Azarenka and No. 5 seed Maria Sharapova advanced to the quarterfinals with wins.
Williams, a four-time winner at the All England Club, saved four match points before the ninth-seeded Frenchwoman closed out the contest by hitting a service winner into the corner. "Beating Serena is almost like a dream come true," Bartoli said. Sharapova advanced by beating Peng Shuai of China 6-4, 6-2