The Taliban have so far not commented on the unprecedented American bombardment on Saturday, authorised by President Barack Obama, in Pakistan's remote southwestern province of Balochistan.
The apparent elimination of Mansour, who swiftly consolidated power following a bitter Taliban leadership struggle over the past year, could spark new succession battles within the fractious movement.
Taliban leader Mansour: man of war, not peace talks
"Mansour was the target and was likely killed" in the remote town of Ahmad Wal by multiple unmanned aircraft operated by US special operations forces, an American official said Saturday.
Afghan President Ashraf Ghani's office on Sunday confirmed the strike, adding that they were investigating whether Mansour had in fact been killed.
The deaths of Taliban leaders have often been falsely reported, and Mansour himself was rumoured to have been killed last December.
"The Afghan government is trying to gather details regarding the fate of Mullah Mansour," the presidential palace said in a statement.
"This drone strike shows that terrorists fuelling conflict will not be safe anywhere."
Mansour was formally appointed head of the Taliban in July last year following the revelation that the group's founder Mullah Omar had been dead for two years.
The group saw a resurgence under the firebrand supremo with striking military victories, helping to cement his authority by burnishing his credentials as a commander.
They briefly captured the strategic northern city of Kunduz in September in their most spectacular victory in 14 years. Southern opium-rich Helmand province is almost entirely under insurgent control.
Afghan Taliban leader Mullah Mansour 'killed' in US drone strike in Pakistan
Pentagon spokesman Peter Cook said Mansour had been "actively involved" with planning attacks across Afghanistan, and presented an "obstacle to peace, prohibiting Taliban leaders from participating in peace talks with the Afghan government".
"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," Cook added.
But Mansour's apparent death was not immediately seen as likely to push the Taliban closer to peace talks and could press them to show they are still able to wage an aggressive battle, observers say.
"The war has been going on for so long, the Taliban has so many leaders and so much ability to function at the local level even without strong central guidance, that we would be well advised to keep expectations in check," said Michael O'Hanlon of the Brookings Institution think-tank.
The drone attack comes just days after representatives from the US, China, Pakistan and Afghanistan held another round of negotiations in Islamabad aimed at reviving long-stalled direct peace talks between the Afghan government and the Taliban.
Pressure has been building in recent months for the United States to return to direct attacks on the Taliban, particularly via air strikes.
"We need to take the gloves off those forces already in-country," namely those belonging to the United States and NATO, and authorise air strikes, David Petraeus, the ex-CIA director and former commander of coalition forces in Afghanistan and Iraq, wrote in The Wall Street Journal inn the past week.
NATO ended its combat mission in Afghanistan in December 2014, pulling out the bulk of its troops, although a 13,000-strong residual force remains for training and counterterrorism operations.
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The Taliban, who announced the start of their annual spring offensive last month, have already stepped up their campaign against the Western-backed Kabul government for the season.
If Mansour's death is confirmed, his two newly named deputies -- influential religious leader Haibatullah Akhundzada and Sirajuddin Haqqani -- could likely step up to fill the power vacuum.
They are both seen as close to the Pakistani military establishment, which has historically nurtured and supported the Taliban.
"Mansour's apparent death will trigger fresh infighting and a new leadership succession battle inside the Taliban," Kabul-based analyst Mia Gul Waseeq told AFP.
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