The US military said in a statement on Monday that al-Hamadani had reportedly been responsible for attacks on US and Iraqi troops and was believed to have "facilitated and directed numerous kidnappings, assassinations and other violence".
They said two Iraqi soldiers shot him dead after storming a building and finding him armed with an assault rifle and "displaying hostile intent".
Drive-by shooting
On Sunday, armed men killed Sheikh Khalil al-Maliki, a local leader of al-Sadr's movement, in a drive-by shooting in the southern city of Basra, police said.
Iraqi and US forces have seized or killed hundreds of followers of al-Sadr in recent weeks in a crackdown on militias in the capital and southern Iraq.
British forces have also targeted al-Sadr officials in Basra, detaining a number in raids.
Senior Shia officials close to the Iraqi government say US and Iraqi forces are mounting a campaign to seize leaders in the movement in an effort to quell sectarian violence that is pushing the country towards civil war.