Militants opened fire on the vehicle with assault rifles in Suki village in Mardan, police said.
The driver's assistant told police they had loaded the truck in Karachi with a 10-wheel vehicle destined for NATO troops and were en route to Kabul.
"The driver was killed on the spot. It was a NATO supply truck and was carrying a 10-wheel vehicle for NATO in Afghanistan," Iftikhar Khan, a police official in Mardan, told AFP by telephone.
There was no claim of responsibility for the attack but officials blamed the Taliban.
Pakistan had shut the main northwestern border crossing to NATO supply vehicles on September 30 for 11 days after a cross-border NATO helicopter assault killed two Pakistani soldiers. Scores of NATO supply vehicles were destroyed in gun and arson attack when the border had been closed.
The bulk of supplies and equipment required by foreign troops in Afghanistan is shipped through the Khyber region, although US troops increasingly use alternative routes through central Asia.
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