Isaac grew Tuesday into a hurricane as New Orleans girded for a "big hurt", seven years after Hurricane Katrina devastated the "Big Easy" and killed 1,800 people across the US Gulf Coast.
The National Hurricane Center in Miami warned that the storm's maximum winds had increased to 75 miles (120 kilometers) per hour, just above the threshold for an upgrade from tropical storm to a category one hurricane.
And Isaac was expected to gain power before making landfall later Tuesday.
States of emergency were declared in Louisiana and Mississippi, allowing authorities to coordinate disaster relief and seek emergency federal funds.
Mayor Mitch Landrieu of New Orleans said the city could expect up 16 inches (40 cm) of rain or more because of the slow-moving hurricane.
"We have dodged a bullet in the sense that this is not a category 3 storm," he said, "But a category one at this strength ... is plenty big enough to put a big hurt on you if you fall into complacency. Let's not do that."
US President Barack Obama urged people take the threat seriously, warning of the possibility of major flooding and damage.
"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," Obama said in a televised statement at the White House.
"Now is not the time to tempt fate. Now is not the time to dismiss official warnings. You need to take this seriously," Obama said.
Obama said he had managed a wide-ranging effort by federal and local governments to make preparations.
His appearance was a reminder of the power of an incumbent to intervene at politically advantageous moments, just as Republicans met to nominate Mitt Romney as their candidate for the November presidential election.
The US National Hurricane Center said in an earlier advisory that in some Gulf Coast areas -- such as the Mississippi-Alabama border east to Florida -- a hurricane warning has been replaced with a tropical storm warning.
But a full-blown hurricane warning remained in effect for metropolitan New Orleans, a city known as the Big Easy for its jazz and easy-going life-style.
As of 1800 GMT, the eye of the hurricane was heading northwest and its eye about 55 miles (85 kilometers) southeast of the mouth of the Mississippi, the center said.
Louisiana Governor Bobby Jindal said 28 school districts had closed and the number was expected to rise.
He said the state government had already contacted Washington about getting reimbursed for hurricane-preparation spending -- an allusion to agonizing delays in getting federal help after Katrina blasted the city.
"We sent a letter yesterday to the president. We have learned from past experiences that you can't wait. You have to push the federal bureaucracy," Jindal said.
The streets of New Orleans were eerily empty Monday as smatterings of rain and stiff winds forewarned Isaac's arrival.
Most residents had already boarded up their windows and stocked up on essentials as they prepared to either evacuate or hunker down.
But weak though Isaac was forecast to be, the timing of the storm -- set to arrive on the seventh anniversary of Katrina -- had many here on edge.
"It brings back a whole lot of memories," said Melody Barkum, 56, who spent days stranded on a roof without food or water after Katrina struck. "I'm not afraid. If I can survive Katrina, I can survive this."
Katrina left behind a devastating sprawl of destruction and death when it hit New Orleans on August 29, 2005, and a bungled response by the Bush administration was a black mark on his second term in office.
Thousands of people were left stranded on the roofs of their houses for days after Katrina's powerful storm surge smashed levees long-warned to be inadequate, flooding 80 percent of the low-lying city.
Those who managed to make it to dry land faced deadly violence and looting as the city descended into chaos and officials failed to even provide water and food -- let alone security and medical aid -- in the sweltering heat.
Officials insisted that the billions of dollars spent to reinforce the city's storm levees and pumps will protect the Big Easy from inundation, and Isaac is nowhere near Katrina's strength.
But Isaac will still pack powerful winds expected to knock out power lines and churn up a massive surge of sea water as much as 12 feet (3.7 meters) deep that will roll up across the Gulf Coast.
Mandatory evacuations have been ordered in a number of coastal counties in Louisiana and Alabama, where people typically build their homes on stilts.
The slow-moving and massive storm -- which is about 410 miles (670 kilometers) wide -- could dump as much as 20 inches (51 centimeters) of rain and spawn tornadoes, the NHC warned.
Obama, no doubt mindful of the bungled handling of Katrina by his predecessor George W. Bush, on Monday declared a state of emergency in Louisiana, allowing federal funds and aid to flow to local authorities.
The US Nuclear Regulatory Commission sent extra staff to two nuclear power plants in Louisiana. They are about 20 and 25 miles from New Orleans and Baton Rouge, respectively.
Jindal urged people to prepare for the worst.
"If you are in low-lying areas and are thinking about evacuating, today is the day to do that," he said Monday.
"If you plan on hunkering down at home, today is the day to get supplies. I strongly encourage people not to wait," added Jindal, who stayed away from the weather-delayed Republican National Convention in Tampa, Florida.
Those heeding the call included Tammy Edmondson, who looked anxious as she picked through the grocery shelves at a Target store with her daughter.
Edmondson said she left town ahead of Katrina and that it was a month before she could go home.
"We had a lot of damage -- we're still fixing some of it," she told AFP. "That's why I'm starting to panic."