Michelin announced Tuesday that 494 jobs would have to go at Clermont-Ferrand, the factory where the business was born in 1889.
More than 12,000 people currently work there.
The departures, including 330 from the heavy goods vehicle retreading department, will be voluntary, it said, and it has set aside 55 million euros for their cost.
Another 164 jobs are to be shed in engineering.
The company also announced that it would invest 90 million euros between now and 2020 to convert the site into "hubs of industrial and technical excellence".
Some of the workers whose jobs will disappear may be able to stay with the company, which recently announced its intention to take on 400 manual workers at Clermont-Ferrand over the next three years.