The 27-year-old Dutchwoman, who rides for SD Worx-Protime, completed the 137km ride around Lausanne in three hours, 29 minutes and 11 seconds.
Kim Le Court Pienaar was second and the 2023 champion Demi Vollering was third.
“I can't believe it,” Wiebes said. “The SD Worx-Protime team worked super-hard. Demi attacked, I thought: 'I need to follow'. It was a super-long sprint.
"I'm really happy with the support from the team. It gave me extra energy," Wiebes added.
"The staff fully believed in me while even I had some doubts. I'm super grateful for this."
Norsgaard Bjerg sprints home to take sixth stage of women's Tour de France
The 2025 champion Pauline Ferrand-Prévôt finished eighth while Vuelta winner Paula Blasi was 12th.
Sunday's second stage takes the riders over a 147.9km course rom Aigle to Geneva.
(With newswires)
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