The coach was carrying a club of elderly people on an excursion when it collided with the lorry near the village of Puisseguin among the vineyards of the St Emilion region, east of Bordeaux.
Many of the victims were thought to have died in the fire, according to emergency workers and local authorities in the department of Gironde.
Images shown on French television showed the coach as a charred shell that had been entirely burned.
"I saw a cloud of smoke," said local resident Yvette Seguy on France's i-Tele TV station, adding that it took place on a bend that is known to be dangerous.
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The driver of the coach was thought to be among the dead. The rest of the victims were passengers on the coach, officials said.
Eight people managed to escape the burning coach -- four of them seriously injured, according to a local official.
It was not clear if the lorry driver, who was transporting wood, also died. Unconfirmed reports said he had managed to escape his burning vehicle to help the coach passengers.
"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."
The crash is the deadliest in France since August 1982, when 53 people including 44 children were killed in a motorway pile-up.
Some 60 firemen and 20 fire engines were dispatched to the scene on Friday, supported by helicopters. A psychological crisis cell and information hotline were also set up.
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 has not been ruled out that Hollande might cut short his visit to Greece.
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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, carrying 49 passengers and a driver, departed early Friday from a tiny village of 650 residents near the site of the accident.
Pierre Henri-Brandet, spokesman for the interior ministry, told BFMTV that four people "were extremely severely injured" -- two with burns and two with head injuries.
Four others escaped with only minor injuries.
"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."
Henri-Brandet added that the accident happened just a few minutes after the bus left the village of Petit-Palais-Cornemps.
Details of how the crash happened were still unclear.
"Apparently, the bus slid into a bend," a local shopkeeper from Puisseguin told French radio station RTL. "The truck and bus were in flames. We saw smoke from 10 kilometres away."
The group were part of a club for retired people and were heading south to the nearby region of Landes for a visit.
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