According to officials, all roads in and out are now impassable and have warned evacuated residents to stay away.
About 400 people have been rescued from flood waters in Wilmington, described as an island within the state.
Two of the first known fatalities – a mother and her seven-month son – were reported in Wilmington on September 14.
At least 15 other people are reported to have died in storm-related incidents across North and South Carolina since storm Florence made landfall on September 13.
In Wilmington, with its population of about 120,000, some 400 people have had to be rescued from flood waters, and most of the city remains without power.
The National Weather Service has warned of at least two further days of possible flash flooding in the area before conditions are forecast to improve.
The area is usually best known as a filming location for One Tree Hill and Dawson’s Creek.
Michael Jordan – who is fundraising to help residents affected by the storm – also grew up in the city.
Many roads inside Wilmington are still passable for residents who defied evacuation orders to ride the storm out.
However, a city-wide curfew has been extended after five people were arrested on suspicion of looting from a store in the city on September 15.
According to the National Hurricane Centre, Florence has now weakened into a tropical depression with winds of 35mph.
Some parts of the Carolinas have seen up to 40in of rain since September 13 – and officials have warned river levels are yet to peak in places.
The US coast guard and volunteer boats have been helping people left stricken by rising flood waters across the states.
Officials in North Carolina have said about 900 people have been rescued from floodwaters there, and about 15,000 people are still in emergency shelters.
President Donald Trump has declared a disaster in several North Carolina counties – a move that frees up federal funding for recovery efforts.
He has praised federal and local law enforcement response to the storm on Twitter several times and the White House has indicated he may visit the affected area in coming days.
Power companies are working to restore power to the almost 650,000 homes and businesses that are still without electricity.
The center of the storm is still over North Carolina but is expected to accelerate north before turning to head toward New England on September 18.
Eleven deaths were reported in North Carolina, and at least six have been reported in South Carolina.
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