"This storm will bring destruction", said North Carolina Governor Roy Cooper.
The hurricane centre also said the threat of tornadoes was increasing as the storm neared shore.
Weather Underground meteorology director Jeff Masters said Florence eventually could strike as a Category 1 with winds less than 100 miles per hour (160 kph), but that's still enough to cause at least $1 billion in damage.
Florence's hurricane-force winds were blowing 80 miles (130 kilometers) from its center, and tropical-storm-force winds reached up to 195 miles (315 kilometers) from the eye.
Antonio Ramirez, a construction worker from El Salvador living in Leland, North Carolina, said he planned to ride out the worst of the weather with his dog Canelo.
Schools and businesses closed as far south as Georgia, airlines canceled more than 1,500 flights, and coastal towns in the Carolinas were largely emptied out.
"A storm surge warning means there is a danger of life-threatening inundation, from rising water moving inland from the coastline".
The police chief of Wrightsville Beach suggested that those who made a decision to stay give him their next-of-kin contact information.
"At this point, I'm just riding out whatever they throw my way, and hope it works out for the best", Tominack said.
"From Wilmington to Charlotte, we'll experience between a 500-year and 1,000-year flood event", Trogdon warned in a late-morning briefing.
A tree fell on a homeowner's auto, parked in the driveway as Hurricane Florence made landfall in Wilmington, North Carolina.
"This is an absolute life-threatening scenario".
Officials in the city of Greenville, North Carolina say that flash flooding has begun around their region.
The hurricane has caused more than 555,000 power outages in North Carolina, with almost 65,000 reported in SC, according to website poweroutage.us. "Significant river flooding is expected as a result of excessive rainfall across area hydrologic basins".
In New Bern, Sarah Risty-Davis is one of the residents who opted not to follow a mandatory evacuation order that was issued three days ago.
Within hours of the storm making landfall, officials in Onslow County - which includes the city of Jacksonville, reported "major structural damage to homes, businesses and institutions".
Still, she said, "I think we're going to stay put", noting her neighborhood's past success in avoiding power outages and flooding.
It's now pummeling the coast of North Carolina with 90mph winds and heavy rain, the CNN reported Friday.
"Inland flooding kills a lot of people, unfortunately, and that's what we're about to see", Long added.
Wilmington's airport recorded a 92mph wind gust on Friday morning, the fastest measured since Hurricane Donna hit the city in 1960. The Category 1 storm is expected to move further across parts of North Carolina and South Carolina Friday and Saturday. The National Hurricane Center's forecast is for Isaac "to gradually weaken over the next few days, and could degenerate into a tropical wave at anytime".
Outside of the wind, the broad circulation of the storm will allow for a storm surge north of the center of circulation heading into Friday.
The Weather Channel on Thursday produced a terrifying Hurricane Florence weather forecast using a visualization to simulate what 9 feet of floodwater might look like in North Carolina. Forecasters said the onslaught could last for days, leaving a wide area under water from both heavy downpours and rising seas.