The pileup was reportedly caused when a cyclist slipped in a bend after a sudden downpour, 5 kilometers (3 miles) into a mountainous leg of the race on Saturday.
It was the first major crash of this year's Tour de France and it involved almost all of the teams in the race.
Numerous injuries in stage 14
Up to 25 riders hit the tarmac while traveling at around 50 km/h (30 mph) and 50 more riders were blocked by the incident.
Spain's Antonio Pedrero was carried away on a stretcher and South African cyclist Louis Meintjes was also hospitalized with a broken collarbone.
Shortly after the race resumed, Colombian Esteban Chaves was also forced to quit.
In a separate incident later on Saturday, French rider Romain Bardet and English rider James Shaw crashed during a high-speed descent. Both subsequently pulled out of the race.
The latest incident comes after a recent fatal crash involving Gino Maeder in the Tour de Switzerland last month.