American Jessica Pegula was fancied by many having come to London off the back of winning the Bad Homburg warm-up event, but the world No.3 was KO'd in the first round by unheralded Elisabetta Cocciaretto.
Olympic champion Zheng Qinwen also had many backers after impressing at Queen's, but the Chinese fifth seed lost to Czech Republic's Katerina Siniakova 7-5 4-6 6-1.
It looked as if defending champion Barbora Krejcikova would also go out prematurely when she lost the first set to Alexandra Eala of the Philippines. But the Czech, who is seeded 17th after an injury-hit year, regained her poise to win 3-6 6-2 6-1.
Pegula, who beat Iga Swiatek in straight sets at Bad Homburg, had not lost in the first round at a grand slam since the French Open in 2020.
But Cocciaretto, ranked 116, was unperturbed by her status and form in dismissing the third seed 6-2 6-3 on Tuesday.
The Italian, whose ranking has dipped in recent months, said she had told herself to "be more aggressive and go for it, don't think about losing or winning the point".
The 24-year-old Cocciaretto, who missed Wimbledon last year because of pneumonia, added: "I'm really grateful that now I can play, that now I'm in this big tournament, big stage. I'm just enjoying it."
Pegula, a quarter-finalist at Wimbledon in 2023, hit five winners while making 24 unforced errors.
"For this to happen today, it's disappointing. I don't know how else to put it," she said. "I'm upset that I wasn't able to turn anything around. But at the same time, I do feel like she played kind of insane. Hats off to her. Kudos to her for playing at a high level that I couldn't match today."
Zheng Qinwen had reached at least the quarter-finals in her last three events, Rome Masters, Roland Garros and Queen's, where she made the semi-finals. But this was the Zheng of old as she suffered her third straight first-round exit at Wimbledon.
Siniakova is 81 in the world but no stranger to success being the No.1 ranked doubles player and a three-time winner at the All England Club, including last year alongside Taylor Townsend.
Seven of her 10 major doubles titles were won with Krejcikova who showed the way in singles with her win here last year.
Before settling against Eala, the first Filipina in the Wimbledon main draw in the Open era, Krejcikova looked in danger of following compatriot Marketa Vondrousova last year in surrendering the title at the first chance.
However, another Czech, 15th-seed Karolina Muchova, lost 7-5 6-2 to Xinyu Wang.
Elsewhere seeds Iga Swiatek, Clara Tauson, Mirra Andreeva, Elena Rybakina and Sofia Kenin progressed but Magdelena Frech, Marta Kostyuk and Magda Linette, seeded 25, 26 and 27 respectively, lost to Victoria Mboko, Veronika Erjavec and Elsa Jaquemot.
On her last visit to the lawns of SW19 two-time champ Petra Kvitova said farewell with a 6-3 6-1 defeat to 10th seed Emma Navarro.
with agencies
5°C