The NHC said the first tropical storm-force winds of at least 39 miles per hour (63 kph) would hit the region early on Thursday with the storm's centre reaching the coast Friday.
For people living inland in the Carolinas, the moment of maximum peril from flash flooding could arrive days later, because it takes time for rainwater to drain into rivers and for those streams to crest. Water kills more people in hurricanes than wind, and he said it will still be an extremely risky storm for rain and storm surge.
"Typically, we see a stimulus effect that creates jobs and raises incomes for South Carolinians", said Joseph Von Nessen, a research economist at the University of SC. But forecasters said its extreme size meant it could batter the US East Coast with hurricane-force winds for almost a full day.
The "threat of freshwater flooding will increase over the next several days" in the impacted areas.
Weather Underground meteorology director Jeff Masters said Florence eventually could strike as merely a Category 1 hurricane with winds less than 100 miles per hour (160 kph), but that's still enough to cause at least $1 billion in damage.
As of 11 p.m. EDT Wednesday, the storm was centered 260 miles (455 kilometers) east southeast of Wilmington, North Carolina, moving northwest at 17 mph (28 kph).
Emergency preparations included activating more than 2,700 National Guard troops, stockpiling food, setting up shelters, switching traffic patterns so major roads led away from shore, and securing 16 nuclear power reactors in the Carolinas and Virginia.
"The center of Florence will move over the southwestern Atlantic Ocean between Bermuda and the Bahamas today, and approach the coast of North Carolina or SC in the hurricane warning area on Thursday and Friday", the NHC said.
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The outer bands of the storm were already reaching the coast Thursday, bringing tropical-force winds and rain.
Rescue workers in North Carolina meanwhile were scrambling to save people stranded in their homes. He says: "If Mama and Grandma are going, then a lot of people are leaving".
"We will still be able to respond, but we won't be at our outlying coastal units", Reed said. "Our meteorologists are saying that the rainfall amounts will be devastating in certain areas", he said.
More than 634,000 homes and businesses were without power in North and SC early on Friday, utility officials said. The rainfall will cause prolonged significant river flooding. Combined, North and SC boast an economy bigger than Saudi Arabia's. It was downgraded to Category 1 before coming ashore on Friday near Wrightsville Beach, near Wilmington.
As of Tuesday, more than 1.7 million people in the Carolinas and Virginia were warned to clear out.
The states of Georgia, South Carolina, North Carolina, Virginia, and Maryland have all declared states of emergency ahead of Florence.
After reaching a terrifying Category 4 peak of 140 mph earlier in the week, Florence made landfall as a Category 1 hurricane at 7:15 a.m.at Wrightsville Beach, a few miles east of Wilmington and not far from the SC line.