Cuba evacuated 220,000 people, while residents of southern Florida stocked up on drinking water and gas to prepare for Wilma, which spun off the coasts of Mexico and Belize packing winds of around 240kph.
Described by forecasters as extremely dangerous, Wilma killed 10 people in mudslides in Haiti earlier in the week.
Expensive beachfront hotels all along Mexico's Maya Riviera coast emptied of tourists who escaped to shelters. The normally calm, turquoise Caribbean heaved and frothed and light rain began to fall.
"We are trying to stay calm, but we are freaking out inside," said Kerry Rieth, a tourist from Pennsylvania in the cloud-covered resort of Cancun. Winds were strong and heavy rains were expected later in the day.
Wilma became the strongest Atlantic storm on record in terms of barometric pressure on Wednesday. It weakened to a Category 4 hurricane, then picked up speed again as it headed toward Mexico's Yucatan Peninsula, where it was expected to hit on Friday.
"Believe me, this is still a very, very powerful hurricane," said Max Mayfield, director of the US National Hurricane Centre in Miami.
Mexican resorts emptied out with
tourists heading for shelters
The hurricane season has six weeks left and has already spawned three of the most intense storms on record. Hurricane experts say the Atlantic has entered a period of heightened storm activity that could last another 20 years.
The storm was expected to miss Gulf of Mexico oil and gas facilities battered by hurricanes Katrina and Rita in August and September, but Florida's orange groves were at risk.
"The centre of Wilma will be very near the coastline of the Yucatan by midday tomorrow. However, Wilma has a large circulation, and hurricane conditions will be felt well before the arrival of the centre," the hurricane centre said.
Residents who live in flimsy shacks that cannot withstand high winds were being moved to shelters.
The island of Cozumel, one of the world's best spots for scuba diving, faced a possible direct hit and tourists were ordered to leave. In Cancun, they took shelter at gymnasiums and schools as the storm was expected to send a 10ft surge of water over the coast.
The Mexican authorities said about 42,000 tourists could be evacuated from coastal areas, and airlines added flights from Cancun and nearby points on the Riviera Maya as well as Cozumel and Isla Mujeres.
Forecasters said Wilma would strike densely populated southern Florida late on Sunday.
Many in Florida are evacuating
ahead of Wilma's arrival
At a briefing in Tallahassee, Florida, Governor Jeb Bush told residents to take advantage of the extra time the slow-moving storm has given them to prepare.
"You need to have non-perishable food for 72 hours. Make sure you have fresh water, make sure you have batteries, battery-powered radios and lighting so that you can survive what will happen after a storm."
The authorities in the Keys, connected to mainland Florida by a single road, ordered tourists out on Wednesday and are considering telling the islands' 80,000 residents to evacuate on Saturday.