The pilotless drone fired four missiles at a vehicle, in which Mufti was travelling along with three other militants near Mir Ali village of Miranshah in the restive tribal area.
At least three suspected militants, including Mufti, were killed on the spot while one was injured, a report said.
"Mufti Ali Muhammad was an important leader of the Haqqani network that used North Waziristan as its headquarters for terrorist activities in Pakistan and Afghanistan," a security official said while confirming his death in the drone attack.
The tribal area bordering Afghanistan is considered a hideout of Taliban and Al Qaeda militants. Last year, Taliban chief Baitullah Mehsud was killed in one such air strike.
Since 2004, more than 1,660 suspected militants have been killed in about 200 drone strikes in the area. The US stepped up these strikes in 2010 and more than 700 suspects have been killed in over 100 air strikes this year.
Published 19 November 2010, 16:28 IST