The UMP appeared set to secure more than 60 local councils, exit polls suggested, up from 41.
Marine Le Pen’s far-right National Front also appeared to have made gains, while the ruling Socialists and their allies may lose about 30 departments.
These elections are seen as a test case ahead of 2017’s presidential election.
Paris and Lyon, France’s two biggest cities, were excluded from Sunday’s election.
The National Front appeared to have won a significant number of seats in Sunday’s second round of elections, but it was not clear if it had gained control of any councils, the exit polls said.
Marine Le Pen hailed a “historic” day for the FN, saying: “I thank all our voters for this magnificent success.”
PM Manuel Valls admitted that the Socialist Party had lost ground, and said that the rise in the National Front’s popularity showed a lasting change in France’s political landscape.
He vowed to redouble efforts to boost the economy.
Nicolas Sarkozy said voters had rejected the policies of his successor as president, Francois Hollande.
“Never has our political family won so many councils,” he told supporters.
Francois Hollande has suffered from slumping personal ratings, boosted only briefly by his response to January’s terror attacks in Paris.
French voters have been electing representatives in 101 departments, or counties, charged with issues like schools and welfare.
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