Gradually, Friday through the weekend (local time), the massive storm - containing a zone of tropical-storm-force winds almost 643km wide - will drift inland, engulfing much of SC and southern North Carolina.
In Virginia, where about 245,000 residents were ordered to evacuate low-lying areas, officials urged them to stay in safer locations despite forecast changes showing Florence's path largely missing the state.
As of 2 p.m. EDT, Florence was centered about 110 miles east-southeast of Wilmington, North Carolina, and 165 miles east of Myrtle Beach, South Carolina, moving at 10 mph. "It's a big one", he said at the White House.
Florence could bring life-threatening storm surges, up to 13 feet.
The briefing said Florence "is a large hurricane" with hurricane-force winds extending 80 miles from its center and tropical storm-force winds extending 195 miles from the eye of the storm.
A tropical storm warning is in effect for north of Duck, NC, to Cape Charles Light, VA, and for Chesapeake Bay south of New Point Comfort. This shift to the south certainly brings Charlotte into play for much heavier rainfall, and I think that's going to be the biggest issue that we're going to have to deal with in the Charlotte area is soaking heavy rains that could fall not only over a day but maybe several days after landfall.
A man runs past a mandatory evacuation sign before Hurricane Florence comes ashore in Wrightsville Beach, North Carolina, on Wednesday.
The NHC said the first tropical storm-force winds of at least 39 miles per hour would hit the region early on Thursday with the storm's center reaching the coast Friday. The slow forward motion means Florence will batter the area with heavy rainfall, producing up to 40 inches in coastal North Carolina and northeastern SC.
But what makes Florence so different from other storms this year?
"This rainfall will produce catastrophic flash flooding and prolonged significant river flooding", the briefing said. "But a storm surge of 20 feet could easily wipe this island out".
The National Weather Service said more than 10 million people live in areas under warnings or watches for hurricane- or tropical storm- force winds.
More than 1.7 million people in the Carolinas and Virginia were warned to clear out.
Airlines canceled about 1,200 flights and counting, and some airports in the Carolinas virtually shut down.
Its governor, Roy Cooper, told residents "the time to prepare was nearly over".
Florence has forced people to cut their holidays short along the coast, while the storm's projected path includes half a dozen nuclear power plants, pits holding coal-ash and other industrial waste, and numerous pig farms that store animal waste in huge lagoons. "These enormous waves are produced by being trapped along with very strong winds moving in the same direction as the storm's motion".
Jeff Byard, an administrator at the Federal Emergency Management Agency, said: "Do you want to get hit with a train or do you want to get hit with a cement truck?"
Duke Energy Corp. expected between 25 percent and 75 percent of its 4 million customers would lose power in the Carolinas.