Col. Tom Collins said the airstrike near Musa Qala on Sunday morning killed a senior Taliban leader riding in a car.
Musa Qala on Thursday was overrun by an estimated 200 Taliban fighters who disarmed local police, ransacked the district center and hoisted their trademark white flag.
The town had been subject to a peace deal brokered last October between village elders and the Helmand provincial government that prevented NATO, Afghan and Taliban fighters from coming within 3 miles of the town center.
Collins said the Taliban leader was killed within that 3 miles zone with the approval of the Afghan government. He said no NATO or Afghan forces were on the ground in Musa Qala.
Collins didn't immediately name the person killed in the strike, but Mohammad Wali, a Musa Qala resident, said the airstrike killed a Taliban leader named Mullah Abdul Gafoor and some of his associates while they were riding in a truck through a small village just outside Musa Qala.
Another resident, Lal Mohammad, told The Associated Press on Saturday that the fighters in Musa Qala were being led by Gafoor, the hardline militia's corps commander in western Afghanistan during the Taliban regime.
Musa Qala saw intense battles between Taliban fighters and British troops last summer and fall. The fighting caused widespread damage to the town of around 10,000 inhabitants, most of whom were forced to leave.
British forces withdrew from Musa Qala in October after the truce, which turned over security to local leaders and prevented NATO forces from entering the town.
Gen. David Richards, who was replaced Sunday as NATO's commander, told AP on Saturday that "very surgical and deliberate" force would be used to evict the fighters from Musa Qala, where he said the alliance's strategy of avoiding military action has driven a wedge between residents and Taliban insurgents.