The centre of Tropical Storm Isaac's projected path is heading directly for New Orleans and could make landfall as early as tonight, nearly seven years to the day after Hurricane Katrina devastated the city.
Forecasters said Isaac would intensify into a Category 1 hurricane later today - far less powerful than Katrina in 2005.
Still, residents shuddered and President Barack Obama declared a state of emergency in Louisiana, making funding available for emergency activities.
Isaac, which left 24 dead in Haiti and the Dominican Republic over the weekend, has shifted course from Tampa, Florida, where the Republican National Convention pushed back its start to today in case the storm passed closer to the gulfside city.
Hurricane warnings extended across some 330 miles, from Louisiana to western Florida. The National Hurricane Centre said Isaac was expected to have top winds of around 95mph when it hit land.
Katrina's winds reached a high of more than 157mph when it hit on August 29 2005.
The size of the warning area and the storm's wide bands of rain and wind sparked emergency declarations in Mississippi, Florida and Alabama too. Evacuations were ordered for some low-lying areas, and hurricane-tested residents were boarding up homes and stocking up on food and water.
Federal Emergency Management Agency (FEMA) officials said the updated flood defences around New Orleans were equipped to handle storms stronger than Isaac. Levee failures led to the catastrophic flooding in the area after Katrina, which killed 1,800.
In New Orleans, officials had no plans to order evacuations and instead told people to stay indoors and make do with the supplies they had.
"It's going to be all right," said New Orleans mayor Mitch Landrieu.
As of 8pm local time yesterday (9pm BST), Isaac remained a tropical storm with winds of 70mph. Its centre was about 230 miles south east of the mouth of the Mississippi River and it was moving north west at 10mph.
A tropical system becomes a Category 1 hurricane once winds reach 74mph. Storm surge was considered a major threat.
But not everyone was waiting to see what happened. Shawanda Harris lost everything she owned when her New Orleans apartment was flooded during Katrina. Yesterday her neighbourhood was packing up and leaving. She planned to caravan out of the city with relatives.
"People ain't taking chances now," she said.
She said Isaac was coming - just as Katrina did - at the end of the month, when many people are low on money.
"They got rent to pay. They got bills. Pay day isn't until the end of the month, Friday," she said. "Right now, half our family got money. Some of our family got nothing. That's why we're leaving together."
Fema administrator Craig Fugate said earlier that people should not focus just on New Orleans. "This is not a New Orleans storm. This is a Gulf Coast storm. Some of the heaviest impact may be in Alabama and Mississippi," he said.
If the storm hits during high tide, it could push floodwaters as deep as 12 feet on shore in Louisiana, Mississippi and Alabama and up to six feet in the Florida Panhandle.
The US government said 78% of the oil production in the Gulf of Mexico had been halted in preparation for Isaac. The Bureau of Safety and Environmental Enforcement said about one million barrels per day of oil production had been stopped as companies evacuated 346 offshore oil and gas production platforms - 17% of daily US oil production and 6% of consumption.
The agency said about 3% of daily US natural gas production and consumption had also been affected. Production was expected to quickly resume after the storm passes.
Even though the storm was moving well west of Tampa, tropical storm-force winds and heavy rains were possible because of Isaac's large size, forecasters said.
Republicans briefly opened their convention to order yesterday and then recessed until today.
Before reaching Florida, Isaac was blamed for 19 deaths in Haiti and five more in the Dominican Republic, and it downed trees and power lines in Cuba.