Suspected senior al Qaeda operative Ilyas Kashmiri was the leader of Harkat-ul Jihad Islami (HUJI).
There was speculation he was the mastermind behind last month's rebel siege at a Pakistani naval base.
In that operation in Karachi, a small number of militants held off around 100 security forces, including commandos, for 16 hours.
HUJI carried out a suicide bomb attack on the US consulate in Karachi which killed four people and wounded 48 in March 2006, the US State Department said.
It has labelled Kashmiri a "specially designated global terrorist", and he was on a list of high-profile militants.
The US claimed HUJI has provided fighters for the Afghan Taliban, which is involved in an insurgency against Nato troops in Afghanistan.
The Pakistani's death was another intelligence coup for America after US special forces killed Osama bin Laden in a town close to the capital Islamabad on May 2.
Kashmiri was reportedly seen in a village in the South Waziristan region shortly before five of his supporters were killed in a US drone strike there.
A Pakistani official said of the latest operation: "We are sure that he (Kashmiri) was killed.
"Now we are trying to retrieve the bodies. We want to get photographs of the bodies." Read More