"You, oppressed people of Iraq, let the entire world hear your voice that you reject occupation, destruction and terrorism," he said.
The statement was reported to have been read to worshippers during Friday prayers at a mosque in Kufa, a holy Shia city south of Baghdad.
The statement is the first by al-Sadr since March 14, when he called on his supporters to resist US forces in Iraq through peaceful means.
Al-Sadr's al-Mahdi army group fought US troops in 2004, but has generally co-operated with an ongoing US-Iraqi security push in Baghdad.
But in his statement al-Sadr blamed the presence of US forces in Iraq for the violence, lack of services and sectarian fighting that continues to plague Iraq.
"I renew my call for the occupier [the US] to leave our land," he said in his statement.
"The departure of the occupier will mean stability for Iraq, victory for Islam and peace and defeat for terrorism and infidels."