Hurricane Katrina is pummelling New Orleans with howling gusts and blinding rain, after sweeping ashore over the southern Louisiana coast.
The storm has knocked out power and submerged part of the low-lying city in up to 6ft (2m) of rising water.
Katrina has torn part of the roof of a stadium, where many sought refuge.
Mississippi and Alabama are also being pounded by the violent storm, which weakened as it swept inland, but brought winds of 105mph (170km/h).
The category-two storm flung boats onto Mississippi, flooded roads in Alabama and swamped bridges in Florida.
The National Hurricane Center warned the Louisiana city would be pounded throughout Monday - and the potential storm surge could still swamp the city, which sits some 6ft (2m) below sea level.
"It's capable of causing catastrophic damage," director Max Mayfield warned.
"New Orleans may never be the same."
'I want to live'
Correspondents in the city say walls of water have been running down the skyscrapers like waterfalls.
Palm trees have been felled, shops wrecked and cars hurled across streets strewn with shattered glass.
A police officer told the BBC he had never seen anything like it.
"This is unbelievable," Jonathon Carol said.
Mayor Ray Nagin has said he believed 80% of the city's 485,000 residents have heeded his order for a mandatory evacuation of the city.
Those unable or unwilling to leave are huddled in shelters, as emergency vehicles patrol deserted streets.
Officials warn that the post-hurricane surge could topple the barriers that protect the city and its historic French Quarter.
There are fears New Orleans could be inundated with chemicals from refineries, and human waste from damaged septic systems.
Mayor Nagin said he had received reports that some water had already breached the barricades.
A man in the east of the city said the water in his home was "rising pretty fast".
"Tell someone to come get me please," Chris Robinson said via mobile phone.
"I want to live."
The evacuation claimed three lives, when three nursing home residents died after being taken by bus to a Baton Rouge church.
States of emergency
Mississippi and Alabama have also urged residents in coastal areas to leave their homes.
Katrina recorded a 22-ft (7m) storm surge on Mississippi's coast.
"This is a devastating hit - we've got boats that have gone into buildings," the Gulfport fire chief said.
US President George W Bush has issued a state of emergency in Louisiana and Mississippi, freeing the path for federal aid.
The storm, which formed in the Bahamas, lashed South Florida on Thursday, killing nine people, uprooting trees, downing power lines and causing extensive flooding.
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