Fateh Khan, an ex-leader of the secular Awami National Party, was killed as his car left a petrol station.
It was not immediately clear if he was victim of a suicide attack or of a bomb placed on a motorcycle.
Security forces largely freed Buner from the control of Taliban militants three years ago.
District police chief Jehanzeb Khan told AFP news agency a suicide bomber had blown himself up in front of Fateh Khan’s vehicle, killing the politician and his guards.
Up to five people were also injured in the attack, he said.
According to Pakistan’s Express Tribune, Fateh Khan was a former ANP leader who had recently joined the Qaumi Watan Party.
Fateh Khan was also the head of a local tribal anti-Taliban force.
ANP leaders have been a regular target of the Taliban in this region but that this is the first suicide attack there for several months.
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