Forecasters say Florence, the first major hurricane to take direct aim at the US mainland this year, could batter coastal areas with whipping winds, torrential rain and storm surges as high as 9 feet.
At 5 p.m., Isaac was located about 560 miles east of Barbados, packing maximum sustained winds of 70 miles per hour and storm force winds extending 105 miles from the centre.
Florence is forecast to move slowly over the Carolinas after making landfall Thursday night or Friday, according to the National Hurricane Center.
"This is a very risky hurricane", Mr McMaster said, adding that the evacuation order for coastal counties was "mandatory, not voluntary".
Hurricane Florence has been downgraded to a Category 2 storm but it is still being classed as extremely risky and life-threatening storm.
The first tropical storm-force winds of at least 39 miles per hour (63 kph) were forecast to hit the coast on Thursday. 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.
"We are. coordinating closely with state and local officials to help ensure the safety of our employees and our property prior to the storm's landfall", CSX spokesman Christopher Smith said.
People in areas vulnerable to the unsafe hurricane, particularly those in coastal regions, have fled ahead of the storm.
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Virginia Governor Ralph Northam's office predicted "catastrophic inland flooding, high winds and possible widespread power outages", cautioning that the deadliest risk would come from flooding.
"Do you want to get hit with a train or do you want to get hit with a cement truck?" said Jeff Byard, an administrator with the Federal Emergency Management Agency.
North Carolina, South Carolina, Virginia, Washington, D.C., and Maryland have declared a state of emergency in anticipation of the storm. As of Saturday, about 676,000 homes and businesses were without power in North Carolina, along with 119,000 in SC.
A primary power supplier in the Carolinas, Duke Energy is already warning that some 75 percent of its 4 million customers could lose power - and not just for a few hours.
Forecasters expected some strengthening today, as Florence marches west-north-west at around 13kmh.
The East Coast isn't the only area facing the brunt of a storm.
Tens of thousands of homes and businesses could be flooded in North Carolina alone, Governor Cooper warned.
She said: "Helene is moving up from the Atlantic towards us".
Interestingly, the Atlantic Ocean housed three hurricanes at the same time, that before Tropical Storm Isaac being downgraded from its former hurricane status.