Tropical storm Isaac is barrelling across the warm waters of the Gulf of Mexico and is predicted to strengthen into a dangerous hurricane in the coming hours.
Thousands of people have evacuated Louisiana's coastline, where Isaac is expected to make landfall later as a Category 2 hurricane.
At least 20 people were killed when the storm smashed into Haiti and the Dominican Republic before it swept across the Florida Keys.
People along a 300-mile stretch of coast from the Florida Panhandle to the Louisiana bayou have been warned to take precautions, with many heading for shelter inland.
Louisiana, Mississippi and Alabama have declared states of emergency amid the threat of flooding, which forecasters said could result in flood waters of between six and 12 feet in areas.
US President Barack Obama signed an emergency declaration for Louisiana, authorising federal aid for the state ahead of the approaching storm.
He has asked the Federal Emergency Management Agency to co-ordinate disaster relief efforts with state and local officials along the Gulf Coast.
The storm is expected to make landfall close to New Orleans - just a day ahead of the seventh anniversary of Hurricane Katrina, which devastated the area and killed 1,800 people.
Billions of dollars have been spent shoring up defences which gave way in 2005.
Carpenter John Corll said: "I think the state and local governments are much better prepared for the storm surge and emergencies."
Officials are warning that hundreds of miles of coastline are at risk.
Craig Fugate, administrator of the Federal Emergency Management Agency, said: "This is not a New Orleans storm, this is a Gulf Coast storm. Some of the heaviest impact may be in Alabama and Mississippi."
Billy Cannon, 72, planned to evacuate his home of 30 years on the Alabama coast.
He said: "If it comes in, it's just going to be a big rain storm. I think they overreacted but I can understand where they are coming from. It is safety."
The National Hurricane Centre has predicted Isaac's winds will be between 96mph and 110mph, possibly causing a strong storm surge.
People have been boarding up their homes and supermarkets have been crowded with those stocking up on canned food and bottled water, while long lines have been forming at petrol stations.
Oil companies have evacuated workers and cut production at Gulf offshore rigs in Isaac's projected path.
Hundreds of flights in and out of Miami and Fort Lauderdale in Florida have been cancelled due to strong winds.
"I sense a high level of anxiety," said New Orleans Mayor Mitch Landrieu.
"The timing, as fate would have it, on the anniversary of Katrina has everybody in a state of alertness, but that is a good thing."
Even though the storm has been moving well west of Tampa, Florida, where the Republican Party Convention is beginning today, tropical storm-force winds and heavy rains are possible in the area because of Isaac's large size, forecasters said.
Isaac has already forced changes to the event schedule. The convention has been shortened and some Gulf Coast delegates are staying away.
Tampa Mayor Bill Buckhorn, a Democrat, said the weather would be "squirrely", but predicted the storm would not unduly interfere with the convention.
"We're going to show the world on Tuesday, Wednesday and Thursday what a great place this is," he said.
"As a state and a city, we're going to put on a good show and be a great host for the Republican Party."
Florida, historically the state most prone to hurricanes, has been hurricane-free since it was hit four times each in 2004 and 2005.
In the low-lying Keys, isolated patches of flooding have already been reported and some roads are littered with downed palm fronds and small branches.