Helene hit Florida's Big Bend region as a powerful category four hurricane on Thursday at 11.10pm and left a chaotic landscape of overturned boats in harbours, felled trees, submerged cars and flooded streets.
Florida governor Ron DeSantis confirmed two storm-related deaths.
Georgia governor Brian Kemp said on X that two people in Wheeler County had died after a tornado touched down during the storm, and an ABC News affiliate reported that a firefighter was killed when a tree fell on his vehicle in Blackshear, Georgia.
Police and firefighters carried out thousands of water rescues throughout the affected states, including in Atlanta, where an apartment complex had to be evacuated due to flooding.
Helene came ashore in Florida with 225km/h winds, weakening to a tropical storm as it moved into Georgia early on Friday.
It was carrying maximum sustained winds of 97km/h as of 8am and was forecast to continue shuffling northward toward the Tennessee Valley.
Life-threatening storm surges, winds and heavy rains continued, the NHC said.
The National Weather Service issued flash flood warnings for several counties in Georgia, South Carolina and North Carolina on Friday morning.
"This is a PARTICULARLY DANGEROUS SITUATION. SEEK HIGHER GROUND NOW!" the service said.
The extent of the damage in Florida began emerging after daybreak.
In coastal Steinhatchee, a storm surge - the wall of seawater pushed ashore by winds - of 2.4-3 metres moved mobile homes, the NWS said on X.
In Treasure Island, a barrier island community in Pinellas County, boats were grounded in front yards.
The city of Tampa posted on X that emergency personnel had completed 78 water rescues of residents and that many roads were impassable because of flooding.
The Pasco County sheriff's office rescued more than 65 people overnight.
The US Coast Guard said one of its helicopter crews saved a man and his dog from the ocean on Thursday after his sailboat became disabled off Sanibel Island.
