The storm, which fell from category four to category three on the five-step Saffir-Simpson scale, is expected to strengthen despite it weakening on Wednesday.
President Trump said the federal government and first responders stand ready to assist, but even so, "bad things can happen when you're talking about a storm this size".
The storm looked likely to make landfall on the coast of North and SC but heavy rain was also expected in Virginia to the north and Georgia to the south.
As the storm moves inland, forecasters warned, the surge could cover all but a sliver of the Carolina coast under as much as 11 feet of ocean water, and days of downpours could unload more than 3 feet of rain, touching off severe flooding.
Industrial waste, including toxic ash from power plants, could also be spread by flooding from the massive storm, which has caused mandatory evacuations of coastal areas in both Carolinas and Virginia, the AP reports.
Meteorologists are warning of potentially catastrophic flooding in the area, with isolated amounts of up to 40 inches of rain expected in parts of SC.
The storm made landfall Friday in North Carolina, bringing punishing winds, heavy rain and record flooding that drove some residents to seek shelter in attics or upper floors of homes. He rescinded the order for Beaufort and Jasper counties Tuesday morning, but officials have not ruled out the possibility of another evacuation order.
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A storm surge warning has been issued from South Santee River, SC, to Duck, NC, and the Albemarle and Pamlico Sounds.
At 5 p.m., Florence was centered about 50 miles (75 kilometers) west-southwest of Wilmington, North Carolina, and about 25 miles (45 kilometers) northeast of Myrtle Beach, South Carolina. Michael Walden, an economist at North Carolina State University, calculates that Florence will deduct about $200 million of output a day from North Carolina's $550 billion-a-year economy until business returns to something close to normal.
Meteorologists are also keeping an eye on yet another tropical disturbance that's spinning in the western Gulf of Mexico. Isaac was moving at nearly 14mph with maximum sustained winds of 40mph as it tracked westward across the Caribbean Sea.
Hurricane force winds extended 80 miles from the centre of the storm, while tropical storm force winds extended up to 195 miles. Hurricane Florence brought a storm surge of some 3 meters (10 feet) as it began battering the USA east coast early on Friday.
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Hurricane Florence making landfall in Carolinas
As of Friday morning, Hurricane Florence made landfall as a Category 1 hurricane and is now soaking the North Carolina coast. The Miami-based center says Florence is bringing "catastrophic" fresh water flooding over a wide area of the Carolinas.
Florence plows inland, leaving 5 dead, states flooded
By Friday evening, the centre of the storm had moved to eastern SC , with maximum sustained winds of 70 miles per hour . A gust of 169km/h was recorded at Wilmington airport, surpassing the power of Hurricane Fran two decades ago.