Isaac's drew new strength early Sunday during a warm-water crossing of the Florida Straits after causing weekend havoc in Cuba, where it downed trees and power lines, and after leaving four dead earlier in Haiti.
On Key West, locals followed time-worn preparedness rituals such as many hunkered down for a lashing Sunday from Isaac swamped the Caribbean and shuffled plans for the Republican National Convention.
"Currently Isaac is a tropical storm that's expected to become a hurricane as it reaches Key West ... then it will move into the Gulf of Mexico and is expected to strengthen" further, said Meteorologist Jessica Schauer with the U.S. National Hurricane Center in Miami.
"Our forecast is that as the system moves northward it is forecast to strengthen to a Category 2," she said, adding an eventual landfall is expected on the northern Gulf Coast. "Definitely the northern Gulf Coast should be preparing for a hurricane right now."
She said Isaac could make a landfall on the northern Gulf Coast late Tuesday night or early Wednesday morning.
A Category 2 hurricane is capable of top sustained winds of 96-100 mph (154-177 kph). But Schauer cautioned that forecasts that far out in time are subject to greater uncertainty. Nonetheless she said a wide swath of the northern Gulf Coast should be bracing for the threat.
Isaac was expected to be at or near hurricane strength by the time its center reached the Keys later Sunday, the hurricane center said.
A hurricane warning was in effect for the Keys, including the Dry Tortuas and for the west coast of Floirda from Bonita Beach south to Ocean Reef, among some other areas, authorities said.
Meanwhile authorities said a hurricane watch has been issued from the mouth of the Mississippi River — not including the New Orleans metro area — eastward to Indian Pass., Fla.
A steady line of cars moved north along the Overseas Highway, the only road linking the Florida Keys, while residents boarded up windows, laid down sandbags and shuttered businesses ahead of the approaching storm. Even Duval Street, Key West's storied main drag, was subdued for a weekend, though not enough to stop music from playing or drinks from being poured.
"We'll just catch every place that's open," said Ted Lamarche, a 48-year-old pizzeria owner visiting Key West to celebrate his anniversary with his wife, Deanna. They walked along on Duval Street, where a smattering of people still wandered even as many storefronts were boarded up and tourists sported ponchos and yellow slickers.
"Category None!" one man shouted in a show of optimism.
When it hits, winds will be "enough to knock you over," National Hurricane Center spokesman Dennis Feltgen said.
The Keys were bracing storm surge of up to four feet, strong winds and the possibility of tornadoes. The island chain's two airports closed Saturday night and volunteers and some residents began filing into shelters.
"This is a huge inconvenience," said Dale Shelton, a 57-year-old retiree in Key West who was staying in a shelter.
As of 5 a.m. EDT, the storm was centered about 205 miles (330 kms) east-southeast of Key West, according to the U.S. National Hurricane Center in Miami. Isaac had strengthened in recent hours, with maximum sustained winds of 65 mph (100 kph) as it gained strength over open water.
The center said a hurricane hunter plane found the top sustained winds had increased from about 60 mph (95 kph) just hous earlier.
The hurricane center said the storm, which was swirling off the northern coast of Cuba overnight, was expected to move near or over the Florida Keys later in the day or Sunday night. Isaac was then forecast to move over the southeast Gulf of Mexico on Monday. It was moving to the northwest toward the Keys at 18 mph (30 kph). Tropical storm-force winds extended outward up to 205 miles (335 kph) from the center, giving Isaac a broad sweep as it passed.
Among the highest-profile potential targets of the storm was the Republican National Convention, set to begin Monday in Tampa. Forecast models show Isaac likely won't hit Tampa head-on, but it could have lashed the city with rain and strong winds just as the convention was ramping up. A tropical storm warning was extended north of Tampa Bay.
Convention officials said they would convene the convention briefly on Monday, then immediately recess until Tuesday afternoon, when the storm should have passed. Florida Gov. Rick Scott, a Republican, declared a state of emergency and canceled his plans to attend convention events on Sunday and Monday.
Isaac has already left a trail of suffering across the Caribbean.
The storm's center made landfall Saturday near the far-eastern tip of Cuba, downing trees and power lines. In the picturesque city of Baracoa, the storm surge flooded the seaside Malecon and a block inland, destroying two homes.
At least four people were reported dead in Haiti, including a 10-year-old girl who had a wall fall on her, according to the country's Civil Protection Office. The government also reported "considerable damage" to agriculture and homes. Nearly 8,000 people were evacuated from their houses or quake shelters and more than 4,000 were taken to temporary shelters.
The Grise River in Haiti overflowed north of Port-au-Prince, sending chocolate-brown water spilling through the sprawling shantytown of Cite Soleil, where many people grabbed what possessions they could and carried them on their heads, wading through waist-deep water.
"From last night, we're in misery," said Cite Soleil resident Jean-Gymar Joseph. "All our children are sleeping in the mud, in the rain."
Scores of tents in quake settlements collapsed. In a roadside lot in Cite Soleil, the dozens of tents and shelters provided by international groups after the earthquake were tossed to the ground like pieces of crumpled paper, and the occupants tried to save their belongings.
"They promised they were going to build us a sturdy home and it never came," Jean-Robert Sauviren, an unemployed 63-year-old father of six said as he stood barefoot in the water and held aloft his arms. "Maybe we don't deserve anything."
Associated Press writers contributing to this report were: Bill Barrow in Tampa; Trenton Daniel and Evens Sanon in Port-au-Prince, Haiti; Peter Orsi and Anne-Marie Garcia in Havana; Fernando Gonzalez in Baracoa, Cuba; and Ezequiel Abiu Lopez in Santo Domingo, Dominican Republic.