Ashraf Ghani, the Afghan President, said the killing of Mansour, who had rejected negotiations, could open the door to talks and called on insurgents to return from Pakistan to join peace efforts. But the strike near Ahmad Wal in Baluchistan instead risks inflaming Taliban anger, according to analysts, with at least one potential successor considered even more opposed to negotiations.
Long-running efforts to kick off a peace process had already been dealt a blow last month after a huge car bomb killed up to 70 people, leading Kabul to declare it would focus on the military defeat of the Taliban.
Thomas Ruttig, co-director of the Kabul-based Afghanistan Analysts Network, said: "There wasn't much of a peace process. There was an attempt to get one going. If you then target their leader, that doesn't really look to me like an invitation to talks."
Pakistan denounced the US drone strike as a violation of its sovereignty.
There is no obvious successor to Mansour. One of his two deputies, Sirajuddin Haqqani, leader of the notoriously brutal Haqqani network, is considered even more implacably opposed to talks with the Western-backed Kabul Government. However, he may lack support in the Taliban's southern heartlands.
John Kerry, US Secretary of State, said the strike sent "a clear message to the world that we will continue to stand with our Afghan partners".
"Peace is what we want. Mansour was a threat to that effort," Kerry said. "He also was directly opposed to peace negotiations and to the reconciliation process. It is time for Afghans to stop fighting and to start building a real future together."
Mansour had formally led the Taliban only since July last year when the death of Mullah Omar was announced, two years after the event. Mansour's appointment triggered infighting in the Taliban, with some commanders accusing him of deliberately concealing Mullah Omar's death from the rank and file so he could issue orders in the dead leader's name.
Several commanders defected, but Mansour went on to head many of the divisions. He oversaw an offensive that temporarily seized the northern city of Kunduz and saw the Afghan Government lose ground across the country.
One senior Taliban commander told Reuters: "There is still complete silence over reports about the killing of Mullah Mansour.
"And if he is dead, then how should the [leadership council] react and announce his killing? Then there is another important task and that's how to choose his successor for the time being."
US officials warned that a leadership shake-up might not necessarily weaken Taliban confidence after recent battlefield successes.
A US intelligence analyst said: "It's hard to see much incentive for them to start compromising now, with the fighting just heating up again."
