The attack was part of a larger NATO effort aimed at retaking a key southern town that the Taleban captured several days ago.
NATO officials say the Taleban commander, Mullah Ghafour, was killed along with an unknown number of Taleban fighters on Sunday morning just outside Musa Qala, in Helmand Province.
NATO Spokesman Colonel Tom Collins told reporters the militant played a central role in last week's raid by the Taleban on the isolated village.
"He should be considered a high level Taleban leader, certainly the key Taleban figure in that area, Musa Qala."
Local residents say hundreds of Taleban militants swept through the remote town Thursday night.
Witnesses say the insurgents destroyed the poorly guarded government center and seized control of the entire village, raising their own flag over the town.
Musa Qala remains at the heart of a long running contest between Taleban insurgents and international forces.
British troops had been defending the town for several months before they agreed to withdraw last October, after the Afghan government brokered a controversial peace agreement with Musa Qala's local tribal elders.
Under that agreement, local officials took responsibility for the town's security while both NATO and Taleban forces agreed to pull out. Then the town fell to the Taleban, prompting the NATO attack to re-take it.
NATO officials say Sunday's attack, which occurred within the so-called demilitarized zone, was coordinated with the Afghan government.
The airstrike comes as US General Dan McNeill assumed command of NATO forces in Afghanistan. He took over NATO's 35 thousand member military force Sunday, in a ceremony in the Afghan capital, Kabul.
He replaces British General David Richards, who led the NATO force for just over nine months. The change of command is part of a regular rotation among NATO member states.
The Taleban were deposed in late 2001 in a US led invasion and have since waged an increasingly deadly insurgency. But NATO leaders say they are capable of dealing them a decisive defeat this year.