Tropical storm Isaac closed in on the US Gulf of Mexico coast on tonight, triggering some mandatory evacuation orders and disrupting US offshore oil production.
It is expected to make landfall between Florida and Louisiana as a Category 2 hurricane.
The wide, slow-moving storm swiped south Florida yesterday and strengthened over the warm Gulf waters.
It is expected to reach land tomorrow night or early Wednesday, the anniversary of devastating Hurricane Katrina seven years ago.
The US National Hurricane Center warned that the storm could push vast amounts of seawater over the shore, flooding the northern Gulf coast with a storm surge of up to 3.6m in some areas.
Isaac was expected to slow down and pour "tremendous amounts" of rain on the region, causing potentially deadly flooding far inland, Hurricane Center Director Rick Knabb said.
"The weather will start going downhill overnight tonight on the northern Gulf Coast," Mr Knabb told reporters on a conference call.
"Wherever it is people are going to be during the storm, they need to get there tonight."
Isaac could hit New Orleans, which is still struggling to fully recover from Katrina, which swept across the city on 29 August 2005, killing more than 1,800 people and causing billions of dollars of damage along the coast.
"That brings a high level of anxiety to the people of New Orleans," New Orleans Mayor Mitch Landrieu told a news conference.
"I want to tell everybody now that I believe that we will be OK," he added.
At 5pm local time (10pm Irish time) today, Isaac was centred 415km southeast of the mouth of the Mississippi River with top sustained winds of 110kph and swirling northwest at 19kph.
It was forecast to strengthen into a Category 2 hurricane on the five-step Saffir-Simpson scale of hurricane intensity, with top winds of 160kph, before moving over the Gulf Coast no later than early on Wednesday.
A tropical storm becomes a Category 1 hurricane at 119kph.
"Strengthening is expected to continue right up until landfall occurs," the National Hurricane Center said.
The storm was more than 645km wide and Craig Fugate, director of the Federal Emergency Management Agency, said the worst effects may well be in Mississippi and Alabama.
"This is not a New Orleans storm. This is a Gulf Coast storm," Mr Fugate said.
The governors of Louisiana, Mississippi and Alabama declared states of emergency and mandatory evacuation orders went into effect for residents of several low-lying districts outside New Orleans and its new flood-protection system.
About 8,000 to 10,000 residents of Mobile, Alabama, were also told to evacuate, as well as nearby Dauphin Island.
Energy producers in the Gulf shut down some of their operations ahead of what could be the biggest test for US energy installations since 2008, when Hurricanes Gustav and Ike disrupted offshore oil output for months and damaged onshore natural gas processing plants, pipelines and some refineries.
The ports of Mobile and New Orleans were closed today and barge traffic was suspended along southern portions of the Mississippi River.
President Barack Obama approved Louisiana's request for a federal disaster declaration, Governor Bobby Jindal said.
Mr Obama's approval, given in a phone call that also included governors of Mississippi, Alabama and Federal Emergency Management Agency Administrator Craig Fugate, makes federal funds available for disaster recovery activities like clearing debris.
In New Orleans, which sits below sea level, long lines formed at some gas stations. In Gulfport, Mississippi, as in many other coastal towns, people crowded supermarkets to buy bottled water and canned food.
Colonel Edward Fleming, commander of the US Army Corps of Engineers overseeing New Orleans flood protection, said improvements to the system put the city in a far better place than it was seven years ago.
But in low-lying Plaquemines Parish, which could be the first to be lashed by Isaac's winds and storm surge, workers scrambled to stack sandbags and reinforce levees.
The parish, which stretches southeast from New Orleans, is cut in two lengthwise by the Mississippi River as it flows to the Gulf of Mexico. Much of the area lies outside the greater New Orleans levee system, and construction projects to bolster protection are not yet complete.
Isaac killed at least 20 people and caused significant flooding and damage in Haiti and the Dominican Republic before skirting the southern tip of Florida yesterday.