(Adds Cuba details, updates death toll, cost to French territories)
* Florida orders evacuation of 5.6 million residents
* Trump warns of "historic destructive potential"
* Coastal flooding hits northern Cuba
* Gasoline hard to find in parts of Florida
REMEDIOS, Cuba, Sept 9 (Reuters) - Hurricane Irma pounded Cuba's northern coast on Saturday as it headed for Florida, where millions of residents were told to evacuate after the storm killed 22 people in the Caribbean and left devastation in its wake.
Still a Category 5 storm when it crashed into Cuba in the early hours of Saturday, Irma weakened slightly as it tore along the island's northern coastline, downing power lines, bending palm trees and sending huge waves crashing over sea walls.
Maximum sustained winds dropped to around 130 miles per hour (215 km per hour) by 8 a.m. (1200 GMT) on Saturday, the U.S. National Hurricane Center (NHC) said, ranking it a dangerous Category 4 storm, the second-highest level.
However, the NHC said Irma would regain strength as it moved away from Cuba and was expected to remain a powerful hurricane as it approaches Florida, arriving in the Keys on Sunday morning.
One of the fiercest Atlantic storms in a century, Irma is expected to cause major damage due to high winds and flooding to the fourth-largest U.S. state by population.
The destruction along Cuba's north central coast was similar to that seen on other Caribbean islands over the last week as Irma plowed into Ciego de Avila province around midnight.
State media said it was the first time the eye of a Category 5 storm had made landfall since 1932. In the days before Irma struck, the island's Communist government evacuated tens of thousands of foreign tourists from resorts on the northern coast.
In Ciego de Avila province, Irma was forecast to generate waves of up to 7 meters (23 feet), with flooding expected as far west as the capital Havana, authorities said on Saturday.
"I am absolutely terrified. I have lived through tropical storms before but nothing like this," said Maybelis Viareal, 30, a receptionist at a hotel in the northern Cuban town of Remedios, as employees frantically tried to barricade doors that were busting open in the winds.
"RUNNING OUT OF TIME"
With the storm barreling toward the United States, officials in Florida ordered an unprecedented evacuation, racing to overcome clogged highways, gasoline shortages and move elderly residents to safety.
With the storm still 225 miles (365 km) south of Miami on Saturday morning, winds and high rains were lashing Florida's largest city.
"We are running out of time. If you are in an evacuation zone, you need to go now. This is a catastrophic storm like our state has never seen," Governor Rick Scott told reporters.
A total of 5.6 million people, or 25 percent of the state's population, were ordered to evacuate Florida, according to the Florida Division of Emergency Management.
The United States has been hit by only three Category 5 storms since 1851, and Irma is far larger than the last one in 1992, Hurricane Andrew, according to the Federal Emergency Management Agency (FEMA).
On Wall Street, the S&P 500 ended slightly lower as investors braced for potential damage and massive insurance claims from Irma. Many economists are predicting that third-quarter gross domestic product will take a hit due to the hurricanes.
President Donald Trump said in a videotaped statement that Irma was "a storm of absolutely historic destructive potential" and called on people to heed recommendations from government officials and law enforcement. In Palm Beach, Trump's waterfront Mar-a-Lago estate was ordered evacuated.
A shelter in southwest Miami filled to capacity just hours after it opened its doors, with many people there remembering the damage caused by Hurricane Andrew, the most destructive to hit the state.
"I'm scared because it is bigger than Andrew," said Ann Samuels, 49. "They say to not stress and not worry, but how can you not?"
MANDATORY EVACUATIONS, GASOLINE SHORTAGES
Irma was set to hit the United States two weeks after Hurricane Harvey, a Category 4 storm, struck Texas, killing about 60 people and causing property damage estimated at up to $180 billion in Texas and Louisiana. Officials were preparing a massive response, the head of FEMA said.
About 9 million people in Florida may lose power, some for weeks, said Florida Power & Light Co, which serves almost half of the state's 20.6 million residents.
Amid the exodus, nearly one-third of all gas stations in Florida's metropolitan areas were out of gasoline, with scattered outages in Georgia, North Carolina and South Carolina, according to Gasbuddy.com, a retail fuel price tracking service.
Mandatory evacuations on Georgia's Atlantic coast and some of South Carolina's barrier islands were due to begin on Saturday. Virginia and Alabama were under states of emergency.
The governors of North and South Carolina warned residents to remain on guard even as the storm took a more westward track, saying their states still could experience severe weather, including heavy rain and flash flooding, early next week.
As it roared in from the east, Irma ravaged small islands in the northeastern Caribbean, including Barbuda, St. Martin and the British and U.S. Virgin Islands, flattening homes and hospitals and ripping down trees.
Irma is seen costing at least 1.2 billion euros ($1.4 billion) in Saint Martin and Saint Barthelemy, a French public reinsurance body said on Saturday.
The French interior ministry said 10 people had been reported dead on the two islands, raising the toll by one.
But even as they came to grips with the destruction, residents of the islands faced the threat of another major storm, Hurricane Jose.
Jose, expected to reach the northeastern Caribbean on Saturday, is an extremely dangerous storm nearing Category 5 status, with winds of up to 150 mph (240 kph), the NHC said.
(Additional reporting by Marc Frank in Havana, Makini Brice in Cap-Haitien, Haiti,; Delana Isles in Providenciales, Turks and Caicos, Bernie Woodall in Ft. Lauderdale, Florida, Ben Gruber and Andy Sullivan in Miami, Bate Felix, Richard Lough and Dominique Vidalon in Paris, Toby Sterling in Amsterdam and Neil Hartnell in Nassau, Bahamas; Writing by Brendan O'Brien in Milwaukee; Editing by Helen Popper and Dale Hudson)