Identified as Usama al-Kini, Al Qaeda's chief of operations in Pakistan, and his lieutenant, Sheik Ahmed Salim Swedan, the two were killed in the missile strike conducted on January 1, said the Washington Post, which first reported the incident quoting an unnamed US counter-terrorism official.
Both men were associated with a string of suicide attacks in Pakistan in recent months and were also on the Federal Bureau of Investigation's most-wanted list for ties to the 1998 bombings of US embassies in East Africa, it said.
Usama Al-Kini is believed by US intelligence agencies to be behind the September 2008 Mariott hotel bombing and also behind the attack on a convoy carrying former Pakistani Prime Minister Benazir Bhutto in 2007, who was later killed in another attack.
"These are two of the most dangerous operational figures in today's Al Qaeda," a US official was quoted as saying by CNN.
There was no immediate confirmation or denial by Central Intelligence Agency. The two Al Qaeda leaders were killed by hellfire missiles fired by a pilotless drone aircraft operated by CIA, the paper said.
"They died preparing new acts of terror," a counter-terrorism expert was quoted as saying by FOX News.
The two were also believed to be involved in the 1998 attacks on US embassies in Kenya and Tanzania, with Kini serving as a central planner.
Czech envoy killed in blast at Marriott hotel in Pakistan
Terror attack in Islamabad
Dramatic footage released of hotel blast