Up to 10,000 people may have to be evacuated from Florida Keys, where Hurricane Irma has blocked the major route and cut power, water and communication lines.
Florida governor Rick Scott said: "My heart goes out to the people in the Keys. There's devastation. I just hope everybody survived. It's horrible what we saw."
Those who chose to ignore warnings to evacuate before the storm are now all-but cut off from the rest of the state - and the US defence department has warned they may yet have to leave.
At the same time, police have put up road blocks to stop the rest of the frustrated 79,000 population from returning to their homes on the devastated islands.
Tony Gibus of Key Largo told the Miami Herald: "I have friends that need help. I have supplies for them."
US Highway 1, which runs from the Florida mainland to Key West, is partially under water and blocked by a large pole.
Bridges connecting the islands need to be checked before they can reopen.
The Florida Keys Aqueduct Authority has issued a boil water notice, but said that while there were water supply issues on the Keys, the main pipeline remained intact.
An announcement by Monroe County reassured residents that help was on the way.
It said: "The wind may have stopped blowing, but for most of the Florida Keys, there is no fuel, electricity, running water, or cell service. For many people, supplies are running low and anxiety is running high."
Emergency services are working their way down the Keys but have reportedly not got further than the Upper and Middle Keys.
Florida Keys felt the fullest extent of Irma when it made landfall as a category four storm with around 200km/h winds on Sunday morning.
An estimated 13 million people across the state are now without power.
In the Jacksonville area, the storm surge brought some of the worst flooding it has ever seen, with at least 46 people pulled from swamped homes.
The Jacksonville Sheriff's Office warned residents along the St Johns River to "get out now".
"If you need to get out, put a white flag in front of your house. A t-shirt, anything white," the office said on its Facebook page.
— City of Jacksonville (@CityofJax) September 11, 2017
Six people in Florida are thought to have died as a result of the hurricane, as well as four in other states.
More than 180,000 are now staying in shelters in Florida as authorities set about a relief effort involving two Navy ships and an aircraft carrier.
There are also reports of curfews in place and authorities checking people's identities. People have been told not to swim at any public beach because of concerns around contaminated water and debris.
Irma has weakened to a tropical depression bringing winds of 55km/h and heavy rainfall.
A1A was blocked from Hurricane Irma damage near Manalapan, Boynton Beach in Florida. Picture by: Sun Sentinel/TNS/ABACA/ABACA/PA Images
In the Caribbean, where 35 people died, the effort to return to normality is likely to take even longer.
St Martin resident Raju Budhrani, 51, said: "The destruction is on a biblical scale. It's how you see it in the movies. It's actually worse than that."
Hundreds of tourists are still trying to leave the once-paradise island, while looting is now a major concern for the locals.
"We can't sleep in peace because of the thieves," said Yovanny Roque, 48.
Another St Martin resident, Germania Perez, said: "There's no food here. There is no water here."
There are also reports of people who are evacuating the island being forced to leave pets behind.
NASA pictures of the Caribbean, taken from space, show the previously lush green islands now turned a dirty brown.
— NASA (@NASA) September 11, 2017
While Hurricane Jose's path is unlikely to make a direct hit on Caribbean islands, it will closely shave the Turks and Caicos islands towards the end of the week, severely hampering the clean-up efforts there.
In Cuba, where the capital's streets are in waist-deep floodwater, President Raul Castro issued a statement to the people, speaking about damage to infrastructure but not mentioning 10 fatalities.
"The storm hit some of our principal tourist destinations but the damage will be repaired before the high season," he wrote.
Food, water and medicine shortages have been reported in the Leeward Islands, which include Antigua, St Lucia, Barbados, Anguilla, the British Virgin Islands.
British Foreign Secretary Boris Johnson is travelling to the Caribbean to oversee relief efforts after huge public pressure and after Dutch and French heads of state announced visits to their overseas territories.