The Washington Post, quoting two people at the well-secured Kandahar home of Ahmed Wali Karzai, 49, reported he was killed by a guard. The report said Karzai had been meeting with tribal elders and politicians and later there were three gunshots in a room where Karzai had gone along with his guard.
Deputy provincial head Agha Lalai Destegeri, who had been meeting with Karzai, said he heard the shots and later found Karzai shot in the head, chest and hand, the Post report said.
The Post reported other guards later entered the room and killed the guard. Karzai died before reaching a hospital, the report said.
CNN, quoting provincial Gov. Tooryalai Wesa, also reported he was shot and killed in his home, but the governor said he did not know what led to the shooting. A spokesman for the governor later said Karzai was killed by a guard.
CNN, quoting the head of Kandahar Hospital, reported Karzai had been shot in the head and chest.
"My brother Ahmed Wali Karzai was killed today," President Hamid Karzai told a news conference scheduled with visiting French President Nicolas Sarkozy, CNN reported. "The Afghanistan people have suffered a lot. Every Afghan family has suffered. I hope one day these sufferings end."
Kandahar is vital to the U.S. forces fighting the Taliban, and the Washington Post, quoting Afghan officials, said the killing could adversely impact the region.
Mir Wali Khan, a former member of parliament from Helmand, described Ahmed Wali Karzai as the No.1 man in Kandahar, the Post said.
"We expect now the security of Kandahar will get worse, and the fighting among the tribes will grow stronger and stronger," he said.
Khan and Destegeri identified the shooter as Sardar Mohammad, the Post reported, adding Karzai employed several guards at his home on a street barricaded by concrete blocks.
Ahmed Wali Karzai's power rose with Hamid Karzai's rise to presidency.
The Post reported Ahmed Wali Karzai had been accused numerous times of being involved in the country's opium trade, but he always denied the allegations.
His home always had visitors including tribal leaders, politicians, U.S. diplomats and soldiers, the report said.
The BBC said critics accused him of being corrupt but his supporters described him as a defender of his Pashtun people. The report said President Karzai always defended him.
Ahmed Wali Karzai, who had survived attempts on his life before, was an ally of the coalition forces in Afghanistan, the BBC said.