The storm has sustained winds of 145mph (230km/h) and is due to make landfall at about midday (16:00 GMT).
Officials warn it is now too late for coastal residents to flee, and that those who remain should seek shelter.
At least 13 people reportedly died in Central America over the weekend as a result of storm rains and floods.
More than 370,000 people in Florida have been ordered to evacuate and move to higher ground, but officials estimate that far fewer have actually left.
"Do not leave your house," Florida Governor Rick Scott said on Wednesday.
"The worst thing you can do now is leave," he said, warning of "unimaginable devastation".