Brock Long, director of the Federal Emergency Management Agency (FEMA), said Irma caused major damage in the Florida archipelago south of Miami, known for boating, scuba diving and fishing.
There have been no reports of fatalities in the Keys since Irma made landfall there as a Category Four hurricane, but the islands have been all-but cut off since the storm struck early Sunday.
"You just pray that everybody is alive," Governor Rick Scott said of the Keys residents -- estimated to number several thousand -- who ignored orders to evacuate.
Despite forecasts of catastrophic damage, most of the Sunshine State appeared to have escaped the worst as Irma raked the western coast of Florida, eventually being downgraded to a tropical storm.
The Keys stands as the major exception.
"Some of the initial estimates are -- and this is why we asked people to evacuate, largely from storm surge -- 25 percent of the houses in the Keys initially have been destroyed and 60 percent have been damaged," Long told a news conference.
"Basically every house in the Keys has been impacted some way or another," the FEMA chief said.
Keys residents were just beginning to make their way home Tuesday, with most of the archipelago still closed to traffic as authorities assess the condition of bridges connecting the single highway that links the islands.
"Returning residents should consider that there are limited services. Most areas are still without power and water. Cell service is spotty. And most gas stations are still closed," Monroe County authorities said in a Facebook post.
With over 15 million people without electricity in Florida, one million in neighboring Georgia and 300,000 in Puerto Rico, authorities launched a massive effort to restore power.
"We're having over 30,000 individuals from out of state helping us get our power back on," Governor Scott told reporters while touring flood damage in the northeast city of Jacksonville.
Scott said the authorities had rescued more than 300 people in Jacksonville, a city of 880,000 which was hit by flooding on Monday.
Before reaching the United States Irma tore through a string of Caribbean islands, going from tiny Barbuda on Wednesday to the tropical paradises of Saint Barthelemy and Saint Martin, the US and British Virgin Islands, Puerto Rico, the Dominican Republic, Haiti and the Turks and Caicos Islands.
Irma's overall death toll is estimated to be at least 40 after Cuba reported that 10 people had been killed there over the weekend.
Macron, Johnson visit Caribbean
French President Macron and Britain's Foreign Secretary Johnson were visiting their hurricane-hit Caribbean territories on Tuesday.
Dutch King Willem-Alexander is already in the region, which bore the brunt of one of the most powerful storms on record and where residents and holidaymakers are becoming increasingly desperate.
Macron's plane touched down in Guadeloupe en route to St Martin, a French-Dutch territory, amid growing frustration about lawlessness there.
"He needs to come to look around, so that he realizes the horror here," local resident Peggy Brun told AFP.
The French, British and Dutch governments have faced criticism for failing to anticipate the disaster with an editorial in The Telegraph newspaper calling the response "appallingly slow."
Speaking in Guadeloupe, Macron insisted French authorities were as well prepared as they could have been.
"Now is not the time for controversy," he said. "Returning life to normal is the absolute priority."
Johnson will visit the British Virgin Islands and Anguilla, where Britain has sent nearly 1,000 military personnel to help both with security, and what he described as an "unprecedented" relief effort.
"The UK is going to be with you for the long term," Johnson said in a video message to island residents, dismissing the criticism as "completely unjustified."
Briton Claudia Knight said her partner Leo Whitting, 38, was stranded on the island of Tortola in the British Virgin Islands.
"Everyone's turned feral and no-one's going out without being armed... It's turning really nasty," she told the Press Association news agency. "Leo carries a knife with him."