Many of the victims were thought to have died in the fire, while the driver of the lorry was also killed, according to fire officials and local authorities in the department of Gironde.
The two drivers were killed, while the rest of the victims were passengers on the coach, officials said.
Images shown on French television showed the coach as a charred shell that had been entirely burned.
The two vehicles collided head-on near the village of Puisseguin north of Bordeaux.
The crash is the deadliest in France since 1982.
"The French government has fully mobilised after this terrible tragedy," President Francois Hollande said from Athens, where he is on an official visit.
"We are plunged into sadness due to this drama," he added.
Five passengers managed to escape from the coach, which had caught fire. Three others were unharmed, local authorities said.
Prime Minister Manuel Valls, Interior Minister Bernard Cazeneuve and Transport Minister Alain Vidalies were also on their way to the site, according to the transport ministry.
It had not been ruled out that Hollande might cut short his visit to Greece to visit the crash site.
Valls expressed his "emotion in the face of this very heavy toll" on Twitter, and promised his "support to the families of the victims".
The coach, which was carrying 49 passengers and a driver, had departed early today from a village near the site of the accident to take its elderly passengers out on an excursion.
"It's an incredible tragedy with an extremely heavy toll. It's a catastrophe," he said.
"They were retired people, elderly people, who were going on a day out," he added.
A statement from the French presidency said the lorry was carrying wood.
In August 1982, 53 people including 44 children were killed in a motorway pile-up in the Cote D'Or region of eastern France.
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