Hurricane Isaac has come ashore in south-eastern Louisiana and is heading towards New Orleans.
Isaac is lashing coastal areas with winds of up to 80mph (130km/h) and it is expected to reach New Orleans exactly seven years after it was hit by Hurricane Katrina.
The city has closed the new floodgates designed to protect it from flooding.
President Barack Obama warned residents in Isaac's path to heed evacuation warnings and not "tempt fate".
Thousands of people have fled the area; many of those who stayed behind have locked themselves indoors.
At 00:00 EDT (04:00 GMT) the centre of the hurricane was estimated to be 65 miles (105km) south of New Orleans and moving at about 8mph (13km/h), the US National Hurricane Centre (NHC) said.
The BBC's Alastair Leithead in New Orleans says roadworks are being pulled apart by winds and trees are being shaken from their roots.
Power cuts have been reported across low-lying parts of Louisiana and Mississippi, affecting more than 200,000 homes and business.
Mr Obama has declared an emergency in Louisiana and Mississippi, allowing federal funds to be released to local authorities.
"I want to encourage all residents of the Gulf Coast to listen to your local officials and follow their directions - including if they tell you to evacuate," Mr Obama said on Tuesday.
Speaking from the White House, he added: "Now is not the time to tempt fate. Now is not the time to dismiss official warnings. You need to take this seriously."
Shortly before Isaac reached hurricane status on Tuesday, Louisiana Governor Bobby Jindal called for the Federal Emergency Management Agency (Fema) to make a full emergency declaration for the state.
'Great wall' of New Orleans
He told reporters that a previous declaration did not allow for the reimbursement for state's expenses from the storm.
"We have learned from past experiences that you cannot wait and you have to push the federal bureaucracy," said Mr Jindal, who cancelled an appearance at the Republican National Convention because of the storm.
New Orleans Mayor Mitch Landrieu said his city was "officially in the fight" on Tuesday, as he confirmed its airport was closed and would not serve as a shelter.
Mr Landrieu said that a 26ft (8m) high levee gate that now protects the areas of the city that were badly flooded in 2005 - which he dubbed "the great wall of New Orleans" - was closed on Tuesday morning.
"We will not have a Katrina-like event," he said, adding there will still be parts of the city that will likely be flooded.
"Do not let this storm lull you into complacency," he said. "People may be getting bored. It's better to be bored than to get hurt."
Officials have not ordered any evacuations, telling residents to reinforce their homes and stock up on supplies instead.
The bowl-shaped city of New Orleans is particularly vulnerable to storms, with the centre of the city the furthest below sea-level.
Residents are hoping that billions of dollars spent on reinforcing flood defences that failed catastrophically in 2005 will hold this time.
Isaac has killed at least 24 people in Haiti and the Dominican Republic, and caused significant flooding and damage in the Caribbean.
It largely bypassed the Republican convention in Tampa, Florida, but prompted a day-long delay to proceedings there.
The National Hurricane Center warned that a possible combined "storm surge" and high tide would cause flooding in coastal areas along the Gulf Coast.
Water would potentially reach 6-12ft (1.8-3.7m) above ground in south-west Louisiana and Mississippi, 4-8ft in Alabama and 3-6ft in south-central Louisiana.
Isaac is also threatening heavy rainfall of as much as 20in (51cm) in isolated spots, and could spark possible tornadoes along the northern Gulf Coast.