(Adds quotes from Cuba, Miami)
* 'Go now,' Florida governor tells people in vulnerable areas
* 'Historic destructive potential,' Trump warns
* Coastal flooding hits northern Cuba
* Gas hard to find in parts of Florida
HAVANA, Sept 8 (Reuters) - Hurricane Irma lashed Cuba and the Bahamas as it drove toward Florida on Friday after hitting the eastern Caribbean with its devastatingly high winds, killing 21 people and leaving catastrophic destruction in its wake.
Irma, one of the most powerful Atlantic storms in a century, was expected to hit Florida on Sunday morning, bringing massive damage from wind and flooding to the fourth-largest state by population. A historic evacuation, including from areas around Miami, has been made more difficult by clogged highways, gasoline shortages and the challenge of moving older people in the top retirement destination.
The storm could regain strength and hit the Florida Keys as a Category 5 hurricane, the most powerful designation by the National Hurricane Center, with sustained winds of 160 miles per hour (258 km per hour).
The United States has experienced only three Category 5 storms since 1851, and Irma is far larger than the last one to hit the United States in 1992, Hurricane Andrew, according to the Federal Emergency Management Agency (FEMA).
"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, adding that the storm's effects would be felt from coast to coast in the state.
U.S. 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.
Irma, currently a Category 4 storm with winds of 155 mph (250 kph), was about 345 miles (555 km) southeast of Miami, the National Hurricane Center (NHC) said in its latest advisory.
Cuba was periodically drenched with rain and wind from the outer edge of the storm. Irma was forecast to bring dangerous storm surges of up to 20 feet (6 meters) to the southeastern and central Bahamas and up to 10 feet (3 meters) on parts of Cuba's northern coast.
Cuba's Communist government has traditionally made rigorous preparations when the island is threatened by storms, and the country was at a near standstill as Irma began to drive up the northern coast from east to west.
Irma was forecast to move closer to land as it passed the center of Cuba later in the day and on Saturday, when it could seriously damage resorts on vulnerable keys. Tourists, and even the dolphins that entertain them, were evacuated. The storm was then predicted to veer north, sparing western Cuba and Havana.
In the Cuban fishing town of Caibarien, residents secured their roofs and moved belongings from low-lying coastal areas to houses higher up inland as the skies clouded over. Most said they were worried but well prepared.
Residents in the central province of Camaguey hunkered down on Friday night for the arrival of the storm. There are really strong gusts of wind. It is pouring off and on, and the lights are out, Anaida Gonzalez, a retired nurse, said by telephone.
"DON'T BE COMPLACENT"
Irma was set to hit the United States two weeks after Hurricane Harvey 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, the biggest power company in Florida serving 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.
In Miami-Dade County alone, Mayor Carlos Gimenez said authorities had asked about 660,000 residents to evacuate, adding that this was the largest evacuation he could remember in the county.
Supermarkets in Miami were full of shoppers picking up last-minute supplies and food, and long lines of cars wrapped around the few gas stations still open.
People seeking shelter recalled Hurricane Andrew in 1992 as they braced for Irma.
A shelter in southwest Miami filled to capacity just hours after it opened its doors. People packed into a gymnasium were thinking about the past while worrying about the future.
"I'm scared because it is bigger than Andrew," said Ann Samuels, 49, as she arrived to the Robert Morgan Education Center. On the short trip from her home she said her mind went back to 1992 when Hurricane Andrew forced her and her two young children and eight others into a closet. "They say to not stress and not worry, but how can you not?" she added.
Steve Ortega, 29, decided to go home after peeking into the packed shelter. He was 5 years old when Andrew damaged his home.
"I will never forget the noise. That ... was the scariest thing I ever heard in my life," adding he was worried but optimistic his home would remain standing through Irma.
A mandatory evacuation on Georgia's Atlantic coast was due to begin on Saturday, said Governor Nathan Deal, who expanded a state of emergency to include 94 of 159 counties as the storm's predicted track shifted west. Virginia Governor Terry McAuliffe on Friday added his state to those under a state 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.
On Wall Street, the S&P 500 ended slightly lower as investors braced for potential damage from Irma as it moved toward Florida. Many economists are predicting that third-quarter gross domestic product will take a hit due to the hurricanes.
HURRICANE JOSE REACHES CATEGORY 4
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.
Even as they came to grips with the massive destruction, residents of the islands hit hardest by Irma faced the threat of another major storm, Hurricane Jose.
Jose, expected to reach the northeastern Caribbean on Saturday, was an extremely dangerous Category 4 storm, with winds of up to 150 mph (240 kph), the NHC said on Friday.
(Reporting by Makini Brice in Cap-Haitien, Haiti; Delana Isles in Providenciales, Turks and Caicos; Sarah Marsh in Caibarien, Cuba; Marc Frank in Havana; 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; Neil Hartnell in Nassau, Bahamas; Brendan O'Brien in Milwaukee; Susan Heavey, Doina Chiacu and David Shepardson in Washington; Colleen Jenkins in Winston-Salem, North Carolina; Bernie Woodall in Ft. Lauderdale, Florida; Writing by Frances Kerry and Lisa Shumaker; Editing by Jonathan Oatis and Cynthia Osterman)