"Life-threatening freshwater flooding is likely from a prolonged and exceptionally heavy rainfall event, which may extend inland over the Carolinas and mid-Atlantic for hundreds of miles as Florence is expected to slow down as it approaches the coast and moves inland", the NHC warned.
Officials say that the storm will likely strengthen.
Meanwhile, a storm surge watch was sent out for Edisto Beach in SC to the North Carolina-Virginia border as well as Albemarle and Pamlico Sounds, including the Neuse and Pamlico Rivers.
Hurricane Florence, a potentially catastrophic storm barreling toward the southeastern US, has intensified further north than a typical storm of its size. It is expected to intensify to near Category 5 status as it slows over very warm ocean water near North and SC.
"While some weakening is expected on Thursday, Florence is expected to be an extremely risky major hurricane through landfall", forecasters said. That was Hurricane Hazel, which was already responsible for killing 1,000 people in Haiti and had winds clocked at 150 miles per hour when it hit the coast in 1954.
In the case of Florence, there was an upper-level trough that helped to fuel the monster hurricane's rapid intensification.
Forecasters have predicted as much as 20inches of rain in parts of North Carolina, which could cause potentially fatal flooding.More news: FIFA Loot Boxes Lead to Investigation of EA by Belgian Government
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By way of comparison, the maximum intensity of Hurricane Maria, the storm system which path of destruction left nearly 3,000 people dead in Puerto Rico, was 277.8 km/h, (150 knots), the NHC said.
NHC director Ken Graham admitted: "This one really scares me. All you have to do is look up at your ceiling and think about 12ft of water - that, folks, is extremely life-threatening".
Ahead of Florence's arrival, barrier islands were already seeing risky rip currents and seawater flowed over a state highway, the harbinger of a storm surge that could wipe out dunes and submerge entire communities.
In addition to thousands of homes and businesses, five military bases and half a dozen nuclear power plants are also in the path of the storm.
"I'm prayed up and as ready as I can get", Steven Hendrick said as he filled up gasoline cans near Conway, South Carolina.
"The largest threat to life from hurricanes is not the high winds".
Those in states where the Category 4 hurricane is expected to make direct landfall may have to wait weeks before power is restored, FEMA Associate Administrator Jeff Byard said in a call Tuesday with reporters. American Airlines is also letting travelers in the Caribbean change tickets ahead of Tropical Storm Isaac.