With Irma set to hit Florida as early as Saturday, FEMA Administrator Brock Long warned at a news conference that parts of Florida would be out of electricity for days, if not longer, and that more than 100,000 people may need shelter.
"Hurricane Irma continues to be a threat that is going to devastate the United States in either Florida or some of the Southeastern states," Long said.
Irma had been a Category 5 hurricane before being downgraded to Category 4 early on Friday after pummeling islands in the Caribbean. The United States has experienced only three Category 5 storms since 1851 and Irma is far larger than the last one to hit the United States in 1994, Hurricane Andrew, Long said.
He warned people not to ignore evacuation orders.
"They need to get out and listen and heed the warnings," Long said.
Officials have thousands of personnel ready to respond and millions of meals and liters of water in place nearby, Long said.
The National Weather Service said Friday was the last day to evacuate before winds would start to hit unsafe speeds in Florida.
Airlines said on Thursday they were adding extra flights from Florida before announcing plans to halt service from some southern Florida airports starting Friday afternoon.
Health and Human Services Secretary Tom Price called Irma a "remarkably dangerous storm and the window to get yourself in the right spot ... is closing rapidly."
Price said the main hospital in St. Thomas in the Virgin Islands was closing after damage from Irma and critical patients were being evacuated to Puerto Rico or other islands.