Dutch rider Demi Vollering produced a superb sprint to claim her first La Course title in a thrilling finish in Landerneau.
Anna van der Breggen made a strong attack before Team SD Worx teammate Vollering took the title in a tense finish to the 107.7km race.
Danish rider Cecilie Uttrup Ludwig took second place with two-time winner Marianne Vos in third.
Britain's Lizzie Deignan, who edged out Vos to win in 2020, finished ninth.
It is the continuation of a stellar season for Vollering, who won Liege-Bastogne-Liege earlier this year before second-place finishes at Amstel Gold and Brabantse Pijl.
A 12-strong group of riders was caught with 5km remaining, teeing up a gripping finish at the final ascent of the Cote de la Fosse aux Loups.
While Jumbo-Visma's Vos looked strong in the closing stages, Vollering emerged from her compatriot's slipstream to take the win with a time of two hours 50 minutes 29 seconds having been led out by SD Vorx team-mate Van der Breggen.
"I was not expecting that from today," said Vollering, who finished third in the 2020 race. "I was really looking forward to today, but it was an awesome race.
"[Van der Breggen] did it again because Vos was going all the way to the right, I was a little bit stuck but Anna forced Marianne to go and I could go in Marianne's slipstream.
"It gives me much confidence for the future. Especially now I won this race I'm really looking forward to next year."
In 2022, the one-day race will be replaced by an eight-day women's Tour de France, which is scheduled for 24-31 July, the first time it will have taken place since 1989.
La Course results
1. Demi Vollering (Ned/SD Worx) 2hrs 50 mins 29 secs
2. Cecilie Uttrup Ludwig (Den/FDJ Nouvelle Aquitaine Futuroscope) Same time
3. Marianne Vos (Ned/Jumbo-Visma)
4. Anna van der Breggen (Ned/SD Worx)
5. Grace Brown (Aus/Team BikeExchange)
6. Katarzyna Niewiadoma (Pol/Canyon-Sram)
7. Soraya Paladin (Ita/Liv Racing)
8. Liane Lippert (Ger/Team DSM)
9. Lizzie Deignan (Gbr/Trek-Segafredo) +4 secs
10. Sofia Bertizzolo (Ita/Liv Racing)