Officials from the central province of Ghazni said around 125 people were on board the two buses when they smashed head on with a tanker travelling in the opposite direction.
All three vehicles were quickly engulfed in flames and army units were called to the scene to help with the rescue mission.
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Jawid Salangi, a spokesman for the governor of Ghazni, said some of those taken to hospital were critically injured.
The buses had been travelling from Kabul to Kandahar, in southern Afghanistan, when the crash happened, Mr Salangi added.
Jawid Salangi, a spokesman for the governor of Ghazni, said some of those taken to hospital were critically injured.
The buses had been travelling from Kabul to Kandahar, in southern Afghanistan, when the crash happened, Mr Salangi added.
Pictures of the aftermath show some of the injured walking to hospital in Ghazni.
Most have suffered severe and disfiguring burns.
Photographs from the scene posted on social media showed columns of thick black smoke rising into the air over the burned out wreckage of the buses.
Afghanistan is notorious for its dangerous highways, but even by its own poor safety record this is one of the worst accidents in recent memory.
However there is no suggestion the tragedy was anything other than an accident, Mr Salangi said.