Hurricane Michael has strengthened to a category two storm, with winds topping 100mph (155km/h) as it churns towards the Florida coast.
The storm is expected to reach category three before making landfall on Wednesday.
Governor Rick Scott warned residents to get out of the way, saying: "This is a monstrous storm."
At least 13 people have already been reported killed in Central America as a result of Hurricane Michael.
Forecasters say some regions of the US may see 12in (30cm) of rain, and storm surges of up to 12ft (3.6m).
Is it expected to crawl up the US East Coast after making landfall on the Gulf Coast.
Heavy rains is forecast for the Carolinas, which were drenched by Hurricane Florence last month.
The US National Hurricane Center in Miami, Florida, warned on Tuesday that warm waters will probably further strengthen Michael before it makes landfall.
Over 300 miles of coastline are currently under threat, the National Weather Service has said.
The agency warned residents in Florida and Alabama of possible storm surges, high winds and flash flooding.
Governor Scott warned in a news conference that Hurricane Michael is a "massive storm that could bring total devastation to parts of our state, especially in the panhandle".
He added that it is predicted to be "the most destructive storm to hit the Florida panhandle in decades".
Some 120,000 people have been warned to evacuate along Florida's coast, where schools and state offices are to remain shut this week.
Gov Scott warned of more evacuations due to the size of the potential storm surge.
"No one's going to survive" such a wall of water, he said.
The neighbouring state of Alabama has declared a state of emergency.
The storm caused widespread destruction in Central America over the weekend, where at least 13 people have been reported dead.
According to the Associated Press, six people were killed in Honduras, four in Nicaragua and three in El Salvador.
Western Cuba, including Havana, was struck by Hurricane Michael on Monday
Parts of western Cuba, which was hit by the storm on Monday, were forecast to receive up to a foot of rain.
Offshore oil platforms in the Gulf of Mexico have evacuated workers, halting nearly a fifth of daily production.
Five drilling rigs have been moved out of the storm's path, according to the US Bureau of Safety and Environmental Enforcement.