The DGAC civil aviation authority has asked airlines to cancel some of their flights to ensure there are enough controllers on duty.
The strike affected air traffic across Western Europe.
READ ALSO: Will there be more French air traffic control strikes this summer?
Ryanair, Europe's largest airline, said on Thursday it was forced to cancel 170 flights, affecting 30,000 passengers.
"Once again, European families are being held hostage by French air traffic controllers," said Ryanair CEO Michael O'Leary.
The Airlines for Europe association, which includes Ryanair, Air France-KLM, Lufthansa, British Airways and EasyJet, described the action as "intolerable".
According to sources familiar with the matter, 270 air traffic controllers out of a total workforce of around 1,400 went on strike.
UNSA-ICNA, the second biggest labour group in the sector, launched the action to demand better working conditions and more staff. It was joined by the third largest union, USAC-CGT.
Shortly after 10 am on Thursday, flights were experiencing significant delays, including an average of 1.5 hours for arrivals and 1 hour for departures in Nice, France's third-largest airport.
A quarter of flights departing from or arriving at Paris Charles de Gaulle and Paris Orly have also been cancelled.
Airports in the south were particularly hit. In addition to Nice, 30 percent of flights have been cancelled in cities including Lyon, Marseille, and Montpellier.
On the eve of the school holidays on Friday, the situation is expected to become even more tense at Paris airports and Beauvais, where the DGAC has ordered a 40-percent reduction in the number of flights.
On Thursday morning, the Eurocontrol monitoring agency warned airlines of "significant" delays in the airspace managed by the air traffic control centres in Marseille, Brest and Reims.
Sources said that business aviation, particularly in Nice and Le Bourget near Paris, has also been significantly affected.
France's transport minister called the unions' demands unacceptable.
"The demands made by minority unions are unacceptable, as is the decision to hold this strike at the start of the holiday season," Philippe Tabarot said on Wednesday.
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