The young Najaf-based Shiite cleric condemned the killing of 87 people, including 31 children, in a suspected chemical attack last week in a rebel-held Syrian town that has been widely blamed on Damascus.
"I would consider it fair for President Bashar al-Assad to resign and leave power, allowing the dear people of Syria to avoid the scourge of war and terrorist oppression," he said in a statement.
The United States fired a barrage of 59 cruise missiles at Shayrat airbase in Syria early on Friday to push Damascus, despite its denials of responsibility.
Sadr, who led a militia that fought the US occupation of Iraq, also condemned the American missile strike, urging all foreign parties involved in the Syria conflict to pull out.
"I call on all sides to withdraw their military assets from Syria so that the Syrian people take things into their own hands. They are the only ones with the right to decide their fate -- the alternative will turn Syria to rubble," he said.
Several Iraqi Shiite militias, some of them directly supported by Iran, are helping Assad's camp in the Syria conflict by sending fighting units across the border.
Sadr, however, is seen as a nationalist. His forces have focused on protecting the holy sites and his drive against corruption and nepotism has drawn support from beyond his traditional base.
The Iraqi government on Friday condemned the suspected chemical attack and said it supported any initiative aimed at punishing those responsible.
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