Fire swept through the bus after the pre-dawn crash on a thoroughfare west of the capital, Ouagadougou, regional official Maize Compaore said.
At least 60 people were dead and others were injured. "It's terrible, incredible," she said by telephone.
There was no immediate word on the cause of the crash. Compaore said the driver of the bus was alive, and had reported more than 80 passengers inside the vehicle when the accident occurred.
"The firefighters are still battling the flames in the bus, with bodies inside," local journalist Moussa Souna told The Associated Press by telephone from the scene nearly eight hours after the crash.
Road accidents are common across West Africa, particularly toward the end of the rainy season when already degraded roads are washed out and potholes fill with water.
Buses are frequently overcrowded and the poorest people often ride to their destinations on the top of trucks moving goods to market, which means death tolls from collisions on the region's narrow roads are high.
Ouagadougou is in the center of landlocked Burkina Faso, about 100 miles north of the border with Ghana.