The fate of Mullah Mansour, who assumed the leadership of the Taliban after the death of Mullah Omar, is not yet known.
The Pentagon said it is still assessing the result of the strike.
"Today, the Department of Defense conducted an airstrike that targeted Taliban leader Mullah Mansour in a remote area of the Afghanistan-Pakistan border region," Pentagon Press Secretary Peter Cook said.
"Mansour has been the leader of the Taliban and actively involved with planning attacks against facilities in Kabul and across Afghanistan, presenting a threat to Afghan civilians and security forces, our personnel, and Coalition partners," he said.
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"Since the death of Mullah Omar and Mansour's assumption of leadership, the Taliban have conducted many attacks that have resulted in the death of tens of thousands of Afghan civilians and Afghan security forces as well as numerous US and Coalition personnel," he said.
Noting that the US troops are in Afghanistan today for the
same reason they deployed there in 2001 - to prevent Afghanistan from becoming a safe haven for global terrorists, McCain said Taliban remains allied with terrorists, including al-Qaeda and the Haqqani network,.
"If verified, the death of Taliban leader Mullah Akhtar Mansour would be an important victory in the fight against terror and welcome news to our military personnel in Afghanistan and the Afghan government," said Senator Bob Corker, Chairman of the Senate Foreign Relations Committee.
"I am thankful for the work our military and intelligence communities are doing to bring justice to those responsible for spreading evil. If Pakistan would play a more constructive role, we could destabilise the Taliban far more rapidly," Corker said.
In July, Mansour succeeded Mullah Omar, one-eyed reclusive long-time head, when it was said that Omar had died two years ago. Omar had led the Taliban from its rise in the Afghanistan civil war of the 1990s.