Its projection suggested the storm could damage nearly 759,000 homes and businesses from Charleston, South Carolina, to Virginia Beach, Virginia.
A National Weather Service forecaster in Wilmington, North Carolina, said: “This will likely be the storm of a lifetime for portions of the Carolina coast.
“And that’s saying a lot given the impacts we’ve seen from Hurricanes Diana, Hugo, Fran, Bonnie, Floyd and Matthew.
“I can’t emphasise enough the potential for unbelievable damage from wind, storm surge and inland flooding with this storm.”
It is forecast to bring 20-40in (50-100cm) of rain and life-threatening storm surges of up to 13ft (4m).
Hurricane force winds will emanate up to 70 miles from the centre of the storm, say meteorologists, meaning the impact may be felt on shore well before Florence makes landfall early on Friday.
National Hurricane Center Director Ken Graham warned that rivers up to 40 miles inland may flood.
Mr Graham said on Wednesday morning the Pamlico and Neuse rivers in North Carolina will see their flows “reversed” as storm surges push water back inland.
He added that half of fatalities during hurricanes are caused by storm surges, and another quarter of deaths are due to inland rains and flooding.
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