BBC reported that the two vehicles are reported to have collided head-on near Libourne, in the Gironde region, east of Bordeaux.
A fire official told the Agence France Presse that the dead were mostly adult passengers on the bus. The lorry driver was also killed.
Both vehicles are said to have caught fire after the collision.
Sud Ouest newspaper says the bus was carrying elderly people who were setting off on holiday, adding that there were just eight survivors. Three of them are injured.
Around 60 firefighters are battling the blaze.