Another 73 people who had been on the buses were wounded in the accident on Sunday morning, which set all three vehicles ablaze, said Jawed Salangi, spokesman for the governor of the eastern Ghazni province.
Records showed the two buses were carrying a total of 125 passengers, Salangi said, and that 52 of them had been killed. The survivors had been transferred to hospitals.
The collision happened on the main highway linking the capital, Kabul, to the southern city of Kandahar. Salangi said the road had been cleared and re-opened early in the afternoon, AP reported.
The buses were travelling one behind the other from Kabul to Kandahar when the accident happened, according to Mohammadullah Ahmadi, director of the provincial traffic department. He blamed the crash on reckless driving.
Ahmadi said local residents helped firefighters and first responders pull survivors from the wreckage.
Road accidents are common in Afghanistan, where roads are often in poor condition and traffic laws are rarely enforced.