Dozens of supporters of Ismail Khan gathered outside his home on Saturday after he was replaced as provincial governor and began chanting slogans against the US and Afghanistan President Hamid Karzai, witnesses said.
Shots were fired by US and Afghan security forces after their convoy was pelted with stones, they added. Two people were killed, four injured and four arrested, hospital officials and police said.
On Saturday, the Afghan Government replaced two governors, including Khan, as leaders jockey for power before landmark presidential elections.
The move was President Hamid Karzai's second against regional leaders who helped the US to drive out the Taliban in 2001, but who have resisted his authority ever since.
Khan, the governor of Herat, was offered a new job as minister of mines and industries, Karzai's office said in a statement.
Khan was unavailable for comment but the US ambassador in Kabul said he had refused the new position.
The government justified the move by citing Khan's record of bringing prosperity to the region, saying his "extensive experience ... as well as his management skills, are useful assets that must be utilised at the national level".
But action against him has been expected since his forces squared off in August against those of a rival commander, Aman Allah Khan, in a burst of vicious factional fighting halted by a US-brokered ceasefire.
President Karzai has struggled to
assert his authority nationwide
The battles left dozens dead and fanned tension between the country's main Pashtun and Tajik ethnic groups, with stories of atrocities committed by both sides.
Aman Allah, a Pashtun, was detained in August after the fighting and is under house arrest in the capital.
Officials said at the time that his detention was "part of a wider plan to take all necessary measures to secure long-term stability in the region".
As governor of Herat, Khan, an ethnic Tajik, earned a reputation as an iron-fisted leader accused by international human rights groups of jailing and torturing political opponents.
The United Nations recently complained that an atmosphere of intolerance in the region could distort the 9 October presidential elections.
The presidential palace made no reference to the election, where Karzai, a Pashtun, is expected to triumph.
Karzai has said recently that regional commanders pose a larger threat to this war-shattered nation's future than the remnants of the ousted Taliban government.
Muhammad Fahim (R), another
Tajik leader, was dropped earlier
Khan is nominally loyal to the central government. But he joined Defence Minister Muhammad Fahim, a fellow commander of the Tajik-dominated Northern Alliance, in stalling efforts to disarm their private armies.
Karzai dropped Fahim from his election ticket in July. Fahim then threw his weight behind a rival candidate. Khan has yet to declare support for Karzai or any of his 17 rivals.
The government said Herat's new governor would be Sayyid Muhammad Khaiekhawa, Afghanistan's ambassador to Ukraine.
It said Khaiekhawa was a "well-known intellectual and figure in the jihad" - the struggle against Soviet occupiers in the 1980s when Khan also rose to prominence.
Separately, the presidential palace announced that it was replacing Ghor governor Muhammad Ibrahim Malikzada - who officials have also implicated in the recent fighting - with Abd al-Qadir Alam. No information on Alam was immediately available.
Malikzada was made an adviser to the Interior Ministry.