The Category 4 storm is likely to produce "catastrophic" flooding in the eastern Carolinas, as well as destructive winds.
The storm is now classified as a "major hurricane", meaning wind speeds are greater than 110 miles per hour.
As of 11pm, Florence was a Category 4 hurricane packing sustained winds of 140 miles per hour (220 kilometers per hour), the Miami-based National Hurricane Center (NHC) said. The latest forecast indicates that Florence could stall over or close to southeast North Carolina Friday, then could drift west or southwest this weekend.
Meanwhile the hurricane is forecast to dump 1ft to 2ft 6in of rain that could cause flooding well inland and wreak environmental havoc by washing over industrial waste sites and farms.
While some said they planned to stay put despite hurricane watches and warnings extending over the homes of more than 5.4 million people on the East Coast, many weren't taking any chances.
When it reaches the coastline, it could sit around for days, unloading life-threatening storm surge, unsafe winds and flooding rain.
Across southeastern North Carolina, north of Cape Fear, Florence could hit so hard that entire areas "may become uninhabitable for an extended period", the center stated.
Mayor Joe Benson of Carolina Beach, a small town near Wilmington with a permanent population of about 6,300, said he believes half of the residents have stayed on the island.
Graphic shows the storm track of Hurricane Florence.
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Communities could lose electricity for weeks, Federal Emergency Management Agency (FEMA) Administrator Brock Long said.
The National Oceanic and Atmospheric Administration's Goes-East weather-monitoring satellite used its lightning mapping technology for a video showing Florence, Tropical Storm Isaac and Hurricane Helene as they traveled across the Atlantic on Tuesday.
"We are sparing no expense".
To whip up a monstrous storm like the one chugging for the Carolinas you need a handful of ingredients - and Florence has them all. It will be more tropical depression at that point.
In South Carolina, traffic in all lanes of Interstate 26 from Charleston to Columbia has been directed away from the coast, South Carolina Gov. Henry McMaster said.
"A motion toward the northwest is forecast to begin by this afternoon and continue through Thursday", the hurricane center says. Forecasters also were tracking two other disturbances. That type of rain would cause historic flooding for the region that would occur during the storm and for days after the rain stops due to river flooding.
North and SC and Virginia declared emergencies earlier in the week.
"I'm scared we'll get 30 inches or more of rain", said Carol Trojniar, 69, a longtime Wilmington resident and retired real estate agent who has never experienced a Category 4 hurricane. A steady stream of vehicles filled with people and belongings is moving inland.