A team of religious clerics was hours away from setting off to meet the Tehreek-e-Taliban Pakistan (TTP) with a view to starting peace talks when Mehsud was killed, Nisar told a news conference.
"Brick by brick in the last seven weeks we tried to evolve a process by which we could bring peace to Pakistan and what have you (the US) done?" he said.
"You have scuttled it on the eve, 18 hours before a formal delegation of respected ulema (religious scholars) was to fly to Miranshah and hand over this formal invitation."
Since its creation six years ago, the TTP has killed thousands of civilians, soldiers and police in its bloody insurgency against the Pakistani state.
It was also behind the attempt to kill schoolgirl education campaigner Malala Yousafzai in October 2012.
Nisar said the identity of those killed in the drone strike was "irrelevant".
"The government of Pakistan does not see this drone attack as an attack on an individual but as an attack on the peace process," he said.
Pakistan routinely condemns drone strikes on its soil as a violation of sovereignty and counterproductive to efforts to end militancy, but Nisar's criticism of the US was unusually forthright.