New Orleans Mayor Ray Nagin closed City Hall at noon and ordered a 10 p.m to 6 a.m. curfew to keep streets clear for emergency vehicles. Mississippi officials issued similar curfews in Biloxi and Gulfport.
Streets also are being cleared in the Mississippi cities of Biloxi and Gulfport overnight for emergency vehicles.
Forecasters said Isidore was expected to come ashore along Louisiana's swampy shoreline early Thursday but tropical storm force winds — sustained winds of more than 39 mph — were already hitting the coast as of 8 p.m. EDT Wednesday.
Meanwhile, at least one tornado spawned by Tropical Storm Isidore touched down in Florida, and Gov. Jeb Bush declared a state of emergency for most of the Florida Panhandle.
No injuries were reported from the tornado, which damaged more than a dozen houses and left three homes uninhabitable, said Ed Baltzley, Emergency Operations Center manager for Walton County.
It could be worse. Isidore is much weaker than it was a few days ago.
"This was a very powerful category three hurricane when it struck the Yucatan Penninsula over the weekend. But it stayed there long enough that it really lost that inner core," Max Mayfield, Director of the National Hurricane Center, told CBS News.
CBS News Correspondent Byron Pitts reports on the last-minute preparations for the storm. A few stragglers like Chad Lay ignored Tuesday's evacuation order until late Wednesday. With his wife, daughter and dog, now headed North, he remains more philosophical than frightened.
"Once it gets torn down, just rebuild it. Our life is more important than the material stuff," said Lay.
Isidore was packing much less punch than when it battered Mexico's Yucatan Peninsula as a hurricane over the weekend. The storm was blamed for at least two deaths in Mexico.
As much as 20 inches of rain were forecast in some places, including New Orleans, where the mayor closed City Hall at noon. Schools across the Gulf Coast were also closed, and evacuation notices were posted in such low-lying areas as Alabama's Dauphin Island and Louisiana's Grand Isle.
More than 8 inches of rain fell on parts of Louisiana, Mississippi, Alabama and Florida. Another foot of rain was forecast in some places, including low-lying New Orleans, where drainage pumps were struggling to keep up.
Streets in several neighborhoods were swamped by more than 2 feet of water after rain fell at a rate of 3 inches an hour. At one flooded overpass, a stranded motorist tried to sell cans of beer for $20.
Paul Billiot, 58, of Bayou Du Large, La., arrived at an evacuation center in Houma, southwest of New Orleans, with his 85-year-old uncle, Sydney Lodrigue, who speaks only Cajun French. Lodrigue, who was using a walker, recently underwent heart surgery, Billiot said.
"We don't want to do down there and get caught with him," Billiot said.
The National Guard was called out to help with evacuations in Mississippi and Louisiana, where the governors declared states of emergency. Gamblers were sent home from Mississippi's coastal casinos, and Northrup Grumman shut down its shipyards in Pascagoula and Gulfport.
Bill and Kathy Waite, however, were staying put until last night's sudden storm surge
Says Bill Waite, "that's what gets you trapped. and you can't get out. that water gets up 3 to 4 feet and you're stuck."
According to CBS News Correspondent Mark Strassmann, New Orleans feels menanced by Isidore and is closing its floodgates. The city which sits 15 feet below sea level protects itself with this elaborate system of levies built over the last two centuries.
Meanwhile, a ragged Tropical Storm Lili trekked through the central Caribbean Sea Wednesday, losing some of its punch and easing the threat to Haiti and Cuba.
Forecasters at the National Hurricane Center in Miami had predicted Lili would grow into a hurricane, but the storm's maximum winds fell from 70 mph — Tuesday to just 45 mph — Wednesday.
But with computer models predicting a range of tracks that could take it to Haiti, Cuba, Jamaica or the Bahamas, residents across the northern Caribbean were on alert.
Jamaica's government issued a tropical storm watch for the entire island, telling residents they may see storm conditions within 36 hours.