Maximum sustained winds were at 75 miles per hour, just strong enough to give the storm hurricane status, as of 11:20 a.m. CT, the National Hurricane Center said.
"Hurricane conditions are expected to reach the coast by late afternoon," and the storm's center "should reach the coastline of southeastern Louisiana as early as this evening," forecasters said.
In New Orleans, the Army Corps of Engineers told CNN it was closing the gate to the West Closure Complex, one of the world's largest pump stations, capable of pumping storm water at 20,000 cubic feet per second.
As of 11:20 a.m. CT, Isaac's center was about 160 miles southeast of New Orleans, and about 75 miles south-southeast of the mouth of the Mississippi River, the hurricane center said.
Tropical-storm-force winds extended out as far as 185 miles, and already were battering coastal areas of Louisiana, Mississippi and Alabama, the hurricane center said.
Isaac is moving northwest at 10 mph, and it is expected to slow further, forecasters said, giving it time to wreak havoc in some areas.
Total rainfall could be 14 inches in many places, and isolated parts of southeast Louisiana, southern Mississippi, southern Alabama and the Florida panhandle could get as much as 20 inches, the hurricane center said.
"The combination of a storm surge and the tide will cause normally dry areas near the coast to be flooded," the hurricane center said.
And the storm could spawn tornadoes along the northern Gulf Coast on Tuesday, forecasters said.
President Barack Obama called on Gulf Coast residents to prepare. "Now's not the time to tempt fate," he said. "Now's not the time to dismiss official warnings. You need to take this seriously."
Gusts from the storm were already spreading inland, the hurricane center said.
In Biloxi, Mississippi, popular casinos began to close down Tuesday.
The hurricane center called on people at ports, docks and marinas to "urgently complete" emergency preparations. For people who live on boats, it was time to "make final preparations for securing your craft before leaving it."
"We have a plan in place to secure the city, and we have a plan to respond quickly in the event of emergencies," New Orleans Mayor Mitch Landrieu said. "We're confident that the work we've done in the last few years makes us fully capable of handling this type of storm."
By Tuesday morning, it was too late to evacuate New Orleans, Landrieu said.
Several New Orleans residents told CNN they planned to wait out the storm and were not concerned that the nightmare of Hurricane Katrina in 2005 would be repeated. Isaac is not predicted to bring such dire conditions, and law and order have improved vastly, they said.
If Isaac's landfall comes after midnight, it will hit on Katrina's seventh anniversary.