Tens of thousands of Floridians were hunkering down in shelters for a direct hit from the monster storm, after more than 6.3 million - nearly a third of the state's population - were ordered to evacuate.
For those still at home, it was already too late to escape the wrath of what could be the worst hurricane in storm-prone Florida.
More than 170,000 homes and businesses in Florida have lost power and the centre of Irma is about 140km southeast of Key West.
Florida Power and Light said on its website that more than half of those outages were in the Miami-Dade area, where about 600,000 people have been ordered to evacuate.
"If you have been ordered to evacuate anywhere in the state, you need to leave right now. Not tonight. Not in an hour. Now. You are running out of time to make a decision," Governor Rick Scott said hours before wind gusts began to lash the island chain known as the Florida Keys.
At North Collier Regional Park, a designated shelter just outside the city of Naples, anxious evacuees prayed they and their loved ones would remain safe when the storm made landfall.
"All we wanted to make sure is to feel safe and whatever happens we just have to start I guess from the beginning," Viviana Sierra said.
MacDill Air Force Base, the military installation home to US Central Command, issued mandatory evacuation orders with the eye of the storm expected to pass over its home city of Tampa early Monday. The Kennedy Space Center was also closed.
The White House said President Donald Trump, Vice President Mike Pence and their cabinet were briefed on Hurricanes Irma and Jose, with Trump warning on Twitter that "this is a storm of enormous destructive power".

 Irma weakened from a maximum-strength Category 5 to a Category 3 storm, but then strengthened again to a Category 4, with 210km/h winds, as it approached south Florida.
With near-hurricane force winds lashing the Florida Keys starting around 8:00pm (01:00GMT), the Miami-based National Hurricane Center (NHC) warned that "Irma is forecast to re-strengthen" as it approaches mainland Florida.
There was a serious threat of flooding from storm surges of up to 4.5 metres along Florida's west coast - enough to cover a house.
At least 25 people have been killed since Irma began its devastating march through the Caribbean earlier this week.
Terrified Cubans who rode out Irma in coastal towns after the storm made landfall on Friday on the Camaguey archipelago reported "deafening" winds, uprooted trees and power lines, and blown rooftops.