The project, known as CIGEO, is meant to build an underground storage centre outside the northeastern village of Bure to bury the most dangerous waste from nuclear power plants and hold it for hundreds of thousands of years.
Organisers said 2,000 people had taken to the street in Bure to protest the plan by the National Agency for Radioactive Waste Management (ANDRA) -- though authorities put the number of demonstrators at around 700.
"Get out, ANDRA!" protesters chanted under heavy police presence, marching behind a banner that read "Protest for the Future".
Town officials said another 200 people had joined another, unauthorised protest nearby, many wearing masks and throwing projectiles at law enforcement.
Officers fired tear gas to break up the group, with police helicopters circling overhead.
The national gendarmerie said "weapons and dangerous materials" had been found during searches.
The CIGEO project, launched in 1991, has been contested for decades.
Construction is currently expected to start in late 2027 or early 2028.
France has one of the world's biggest nuclear power programmes, with 18 plants that account for around three-fifths of its electricity output.
Pressure to phase out fossil fuels is driving renewed focus on atomic energy, but managing the radioactive byproducts remains a sensitive issue.
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