The US National Hurricane Centre said the strong Category 3 storm brought with it a potential tidal surge of 6 metres (19 feet), threatening to flood low-lying areas.
Earlier Wilma strengthened into a Category 3 storm as it raced towards the US after causing a trail of devastation through Mexico's Caribbean coast where it left at least seven people dead.
As Florida residents hunkered down for Wilma's arrival, in the Mexican resort of Cancun dazed tourists waded through knee-deep water seeking food and water after three nights in shelters without electricity.
At one point registering as the most intense hurricane recorded in the Atlantic basin, Wilma weakened as it hammered Mexico's Yucatan Peninsula for several days.
It has since strengthened to a Category 3 storm as it headed towards the Florida Keys, where storm-weary residents largely ignored evacuation orders.
"We were all packed and ready to go. But personally, now I feel we will be safe and better off here," said Lori Thompson of Key West, who had considered driving to Orlando.
Emergency managers estimated no more than 7% of the Keys' 80,000 residents evacuated, despite fears they could be stranded if Wilma washed out parts of the Overseas Highway, the only road connecting the 176km (110-mile) island chain to mainland Florida.
"All I can tell people in the Keys who are trying to ride this one out is one of these days your luck is going to run out"
Craig Fugate, Florida director of emergency management
"All I can tell people in the Keys who are trying to ride this one out is one of these days your luck is going to run out," said Craig Fugate, Florida's director of emergency management.
Street flooding and power outages were reported across the Keys early on Monday as the storm neared the area.
Space centre closed
Wilma was expected to cross Florida at its most populous area between Miami, Fort Lauderdale and Palm Beach, which is home to about 5 million people.
Shelters opened and residents of mobile homes and low-lying areas were told to leave.
US space agency Nasa closed its Kennedy Space Centre on the Atlantic coast of central Florida and told its 13,000 workers to stay at home on Monday.
Hurricane Wilma lingered over
the Yucatan Peninsula for days
Wilma caused heavy damage in Mexico, where days of howling winds and torrential rain ruined homes, hotels and shops along the Maya Riviera, which draws millions of tourists to its white-sand beaches, coral-filled seas and Mayan ruins.
"It looks like a war zone out here," said British tourist Thomas Hall as he glanced down an avenue filled with water, fallen trees and other debris.
Soldiers distributed food, but luxury beachfront hotels on a long spit of sand have been cut off by water since Friday.
Four people were killed on Cozumel, a Mexican island known for scuba diving, and another three on the mainland, bringing Wilma's overall toll to at least 17 after mudslides killed 10 people in Haiti last week.
Wilma's heavy rains doused Cuba's tobacco-growing Pinar del Rio province and Havana as it roared past on Sunday. A half-million people were evacuated. Civil defence officials said tornadoes spawned by Wilma injured six people.