Hurricane Isaac has made landfall in southeast Louisiana with winds near 80 mph.
The US National Hurricane Centre said the storm's centre reached land at 7.45pm (23.45 GMT) in Plaquemines Parish, about 90 miles southeast of New Orleans.
The storm's arrival on Tuesday evening comes on the eve of the seventh anniversary of Hurricane Katrina, which devastated the region.
While not as powerful as Katrina, Isaac threatens to flood the coasts of four states with storm surge and heavy rains on its way to New Orleans, where residents have been waiting behind levees fortified after Katrina struck. Isaac also promises to test a New Orleans levee system bolstered after the catastrophic failures during Katrina.
Isaac, a massive storm spanning nearly 200 miles from its centre, zeroed in on New Orleans, turning streets famous for hosting celebrations at all hours into ghost boulevards. Evacuations were ordered in Mississippi's coastal counties and its 12 shorefront casinos were closed.
But hours before the Category 1 hurricane crossed land in Plaquemines Parish, there was little fear or panic. With New Orleans' airport closed, tourists retreated to hotels and most denizens of a coastline that has witnessed countless hurricanes decided to ride out the storm.
Still, Isaac drew intense scrutiny because of its timing with the anniversary of Katrina and the first major speeches of the Republican National Convention in Tampa, Florida, already delayed and tempered by the storm.
"We don't expect a Katrina-like event, but remember there are things about a Category 1 storm that can kill you," New Orleans mayor Mitch Landrieu said, urging people to stay off any streets that may flood.
Other officials, chastened by memories and experience, advised caution. Tens of thousands of people were told to leave low-lying areas, including 700 patients of Louisiana nursing homes. At least one tornado spun off of Isaac in Alabama, but there were no immediate reports of damage or injuries.
Many residents along the Gulf Coast opted to ride it out in shelters or at home. Officials, while sounding alarm about the dangers of the powerful storm, decided not to call for the mass evacuations like those that preceded Katrina, which packed 135mph winds in 2005.