Hurricane Michael has strengthened to a category three storm, with winds near 193kmh as it churns towards the Florida coast, the National Hurricane Center (NHC) says.
Florida Governor Rick Scott has warned residents to evacuate.
Alabama, Florida and Georgia have declared states of emergency in all or parts of the states.
At least 13 people have reportedly died in Central America due to the storm.
Governor Scott called for coastal residents to evacuate, saying: "It could be the difference between life and death."
Alabama is under a state-wide state of emergency ahead of the hurricane, along with 92 counties in southern Georgia and 35 counties in Florida.
Forecasters said some regions of the US may see 30cm of rain, and storm surges of up to 3.6m.
"Strengthening is expected overnight and on Wednesday, and Michael is forecast to be near category four strength when it makes landfall in the Florida Panhandle or the Florida Big Bend area," the NHC said in its latest bulletin.
"Weakening is expected after landfall as Michael moves across the south-eastern United States."
The Florida governor called Michael "a monstrous storm" and urged residents to listen to officials.
It is expected to quickly travel up the US East Coast after making landfall on the Gulf Coast.
Heavy rains are forecast for the Carolinas, which were drenched by Hurricane Florence last month.
North Carolina Governor Roy Cooper told residents: "I know people are fatigued from Florence, but don't let this storm catch you with your guard down."
More than 300 miles of coastline was 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.
Forecasters in Alabama warned of possible tornados.
President Donald Trump told reporters on Tuesday: "We are very well prepared for the incoming hurricane."
Governor Scott warned in a news conference that Hurricane Michael was 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.
Mr Scott warned that he may order more evacuations due to the size of the potential storm surge.
"No one's going to survive" such a wall of water, he said.
On Tuesday, Mr Scott said he activated 2500 Florida National Guard troops in preparation for the storm.
The neighbouring states of Alabama and Georgia have also declared a state of emergency.
Where has Hurricane Michael hit so far?
According to the Associated Press, six people were killed in Honduras, four in Nicaragua and three in El Salvador.
Images on social media showed evacuating families wading through water to get to safety.
The storm caused widespread destruction in Central America over the weekend, where at least 13 people have been reported dead.
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.