Sadr, scion of a family of influential Shiite theologians and a key leader of Iraq's majority Shiites, denounced Maliki's increasingly autocratic regime in stinging terms, stirring the political turmoil as the country heads toward its third post-U.S. invasion national elections.
In a statement issued Tuesday he denounced Maliki's government as corrupt and headed by a "tyrant," a broadside that's likely to inflame Iraq's swirling crisis as many Iraqi Sunnis accuse Maliki of marginalizing and oppressing them.
The cleric's outburst could also sway many Shiites against Maliki's political bloc in the April polls in which the prime minister is seeking a third four-year term.
"Politics became a door for injustice and carelessness," Sadr complained, "and the abuse and humiliation of the rule of a dictator and tyrant who controls the funds, so he loots them ... and the cities, so he attacks them, and the sects, so he divides them."
Maliki is currently floundering, having failed to dislodge al-Qaida forces who seized the cities of Fallujah and Ramadi in the Sunni-dominated western province of Anbar Dec. 30.
An estimated 350,000 people had fled Anbar amid the fighting, in which government forces backed by Sunni tribesmen paid and armed by the state are besieging the two cities with artillery and tanks.
Maliki, locked in a feud with independence-minded Kurds over oil exports, faced another setback Thursday when jihadists of the Islamic State of Iraq and the Levant took over much of the Sunni majority town of Suleiman Bek, 100 miles north of Baghdad.
There's growing violence in the flashpoint northern cities of Mosul and Kirkuk, compounding Maliki's problems as his government faces its worst security crisis since U.S. forces withdrew in December 2011.
Sadr's announcement Sunday that he was withdrawing from politics at such a critical time, and his subsequent denunciation of Maliki could further undermine Maliki, amid fears that he will now escalate his crackdown against political opponents
He has become increasingly autocratic and there are fears he will order his security forces, which he now personally controls, to take harsher measures.
"Maliki could gain or lose a lot depending in how he handles Fallujah," said analyst Michael Knights, an Iraq expert with the Washington Institute for Near East Policy.
"If he does nothing, he looks impotent. At the other end, the Iraqi army could just smash up the city to say it's cleared it of al-Qaida.
"His record over the last four years isn't great. He's launched big arrest operations against the Sunnis every December like clockwork, so it would be unusual and out of character if he handles this with any great sensitivity," Knights told the Middle East Economic Digest.
Sadr has a large Shiite following and he has been held up as a possible alternative to Maliki, but he he has given no sign he plans to challenge Maliki.
The bearded cleric remains a powerful figure, in large part due to the prestige of his family, many members of which, including his father, were assassinated for opposing Saddam Hussein's Sunni-backed regime.
His party controls six ministries in Maliki's government and holds 40 of Parliament's 325 seats.
Sadr was a firebrand opponent of the U.S. occupation of Iraq and twice led insurgencies by his Mehdi Army militia against Americans troops and later against Maliki.
But he has since disbanded the widely feared militia and pursued more moderate political policies.
Sadr supported Maliki in his previous campaigns in the interests of Shiite solidarity and because Maliki controlled more powerful forces. But the relationship has been increasingly tense.
The rift underlines how unstable the Shiite political structure has become. But as Knights observes: "The dirty secret of Iraqi politics is that the Shia are the only group that matters ...
"It doesn't look like there's a perfect combination of Sunnis, Kurds and secular Shias that will remove Maliki.
"It's not political science. It will be decided by the Shia establishment, with some influence from the ayatollahs and from Tehran. At the moment, they seem to want Maliki in place."