The race was marred by crashes and rain near the end.
A chain-reaction accident near the end of the second lap caused many riders to fall. While several riders withdrew, Vos was put 45 seconds behind the reduced peloton.
She eventually caught up and looked set to add to her two golds and five silvers in the event when she broke away with three other riders on the final descent.
But they couldn't outpedal the chasing group, and Ferrand Prevot launched forward to win by a wheel length after 3 1/2 hours.
"I didn't think I won at first, but now I feel fantastic," Ferrand Prevot said. "I had the best team with me. They put me at the front and I didn't crash today. Big thanks to them."
The men's road race will be on the same hilly course around Ponferrada on Sunday.