Six million people -- one third of the state's population -- have been ordered to flee the path of the hurricane, which weakened to a Category Two storm as it churned past the Keys yesterday, packing top winds of 110 miles (177 kilometers) per hour.
At 3:35 pm (1935 GMT), the storm made its second Florida landfall, hitting Marco Island near the popular shopping and golf destination of Naples, hours after striking the Keys island chain.
"Now we have to hunker down and watch out for each other."
After a cabinet briefing from Homeland Security and emergency officials, President Donald Trump said he would travel to the state "very soon."
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"Right now, we're worried about lives, not cost," he said.
Bob Buckhorn, mayor of the low-lying city of Tampa, was blunter: "We are about to get punched in the face by this storm."
One of the mightiest hurricanes ever to slam storm-prone Florida, Irma is threatening dangerous storm surges of up to 15 feet (4.5 meters), enough to cover a house, as it collides with the state after sowing devastation through the Caribbean.
In Miami, the storm brought at least two construction cranes crashing down, while the glitzy Brickell neighbourhood was flooded.
Steven Schlacknam, a 51-year-old visual artist staying in a 37th floor apartment, said the waters were "coming over the sea walls."
"The wooden pier is basically gone," he told AFP.
At least 30 deaths are attributable to the storm, including three in Florida. The US victims included a sheriff's deputy killed in a head-on collision early yesterday as she drove home to get supplies after working in a shelter all night.
Irma closed in on the coast after ripping boats from their moorings, flattening palm trees and tearing down power lines across the Key West island chain popular for fishing and scuba diving.
"There's absolutely no way anybody can be outside right now," Maggy Howes, a first responder on Key Haven, told CNN. "You would not be able to stand or walk."
Irma smacked the Keys 57 years to the day that Hurricane Donna hit the same area in 1960, destroying nearly 75 percent of the island chain's buildings.
"Everything is underwater, I mean everything," Larry Kahn, an editor for local news website FlKeysNews.Com, reported from inside.
The storm also led to some uniquely Floridian responses, with a sheriff forced to warn residents not to shoot at the storm after an online prank promoting the idea went viral.
"To clarify, DO NOT shoot weapons @ #Irma," the office of the sheriff of Pasco County, on the state's west coast, tweeted late Saturday hours before the hurricane made landfall.
At least two towering construction cranes had collapsed downtown, according to residents and details on social media.
Miami, lined with glittering skyscrapers, has about 25 cranes on construction sites of 50 floors or higher, city manager Daniel Alfonso said.
Nearly two million Florida homes and businesses lost power, according to utility company Florida Power and Light, which said it had "safely shut down" one of two nuclear reactors at its Turkey Point power plant.
Before reaching the United States, Irma smashed through a string of Caribbean islands from tiny Barbuda on Wednesday, to the tropical paradises of Saint Barthelemy and Saint Martin, the US Virgin Islands, Puerto Rico, the Dominican Republic, Haiti and the Turks and Caicos.
Terrified Cubans who rode out Irma in coastal towns -- after it made landfall Friday on the Camaguey archipelago as a maximum-strength Category Five storm -- reported "deafening" winds, uprooted trees and power lines, and blown rooftops.
Irma is so wide that authorities faced destructive storm surges on both coasts of Florida and the Keys as Irma follows a path north toward Georgia.
The NHC also warned of tornado risks through last night, with the greatest threat in areas east of the storm's path.
Businesses on both Florida coasts were shuttered.
MacDill Air Force Base in Tampa, the military installation home to US Central Command, issued mandatory evacuation orders ahead of the storm's passage early today, while the Kennedy Space Center on the east coast was also closed.