Ian has strengthened into an extremely dangerous Category 4 hurricane, the US National Hurricane Centre said on Wednesday.
The NHC put the hurricane's location around 125km west-southwest of Naples, Florida with maximum sustained winds of 220km/h.
Ian pummeled Cuba on Tuesday and left the entire Caribbean island nation without power, and was expected to crash ashore into Florida on Wednesday evening south of Tampa Bay, somewhere between Sarasota and Naples.
A Category 4 storm on the five-step Saffir-Simpson scale carries steady winds of up to 209km/h.
The Miami-based NHC warned that Ian would also unleash pounding surf, life-threatening coastal flooding and more than a foot of rain in some areas, as authorities urged more than 2.5 million residents to evacuate their homes for higher ground.
By late Tuesday night, tropical storm-force winds generated by Ian extended through the Florida Keys island chain to the southernmost shores of the state's Gulf Coast, according to the hurricane centre.
The NHC also issued storm surge warnings for much of western Florida's shoreline, predicting coastal flooding of up to four metres from wind-driven high surf.
"The time to evacuate is now. Get on the road," Florida's director of emergency management, Kevin Guthrie, said during a news briefing on Tuesday evening.
Governor Ron DeSantis warned that evacuation would become difficult for those who waited much longer to flee because increasing winds would soon force authorities to close highway bridges.
"You need to get to higher ground, you need to get to structures that are safe," DeSantis said, adding that widespread power outages would leave millions without electricity once the storm strikes.
US Federal Emergency Management Agency chief Deanne Criswell said she worried that too few Florida residents were taking the threat seriously.
"I do have concerns about complacency," Criswell said on Tuesday.
Ian may prove one of the costliest, with data modeling service Enki Research projecting storm-related damages ranging from $US38 billion to more than $US60 billion ($A93 billion).
Ian moved across the southeastern edge of the Gulf of Mexico headed for Florida after thrashing Cuba, knocking out the country's electrical grid and ravaging the western end of the island with violent winds and flooding.
The Florida coastal zone at highest risk for US landfall is home to miles of sandy beaches, scores of resort hotels and numerous mobile home parks, a favourite with retirees and vacationers alike.
Some residents, such as Vanessa Vazquez, 50, a software engineer in St. Petersburg, said they planned to ride out the storm at home despite evacuation warnings.
"I'm staying put," Vazquez said. "I have four cats and I don't want to stress them out. And we have a strong house."
Nearly 60 Florida school districts had canceled classes due to the hurricane, DeSantis said. More than 175 evacuation centres were opened statewide, the governor said, many of them school buildings converted to shelters.
Commercial airlines reported more than 2000 storm-related US flight cancellations, with the St. Petersburg-Clearwater International Airport and Tampa International Airport shut down on Tuesday.
The storm's approach also disrupted the Gulf Coast energy industry, as personnel were evacuated from 14 production platforms and rigs.
