One of the mightiest storms to hit the United States mainland in recent years, Ian flooded Gulf Coast communities before ploughing across the peninsula to the Atlantic seaboard.
Local power companies said more than 2.6 million homes and businesses in Florida remained without power.
Governor Ron DeSantis said that Lee and Charlotte counties, home to more than 900,000 people, were "basically off the grid".
Ian blasted ashore at the barrier island of Cayo Costa on Wednesday afternoon as a Category 4 hurricane with maximum sustained winds of 241 km/h.
After weakening to a tropical storm, Ian was expected to strengthen and make landfall as a hurricane in South Carolina on Friday.
The storm transformed Florida's southwestern shoreline, dotted with sandy beaches, coastal towns and mobile home parks, into a disaster zone as Ian swept seawater into waterfront homes.
"The impacts of this storm are historic and the damage that was done was historic," DeSantis said during a news briefing.
"We have never seen a flood event like this. We have never seen storm surge of this magnitude."
There were two unconfirmed storm-related fatalities, DeSantis said.
The extent of deaths and injuries was unclear on Thursday morning as rescue workers were only starting to respond to calls after not being able to go out during the treacherous conditions.
DeSantis said 28 helicopters were performing water rescues.
He also said the bridge to Sanibel Island - a barrier island on the Gulf coast - was severely damaged and impassible.
Two area hospitals were evacuated, with patients moved to higher ground.
By midday on Thursday, residents in hard-hit areas like Venice, located in Sarasota County about 120km south of Tampa, hunted for family and friends while rescue crews worked to reach people trapped in flooded homes.
Kurt Hoffman, sheriff of Sarasota County, told residents in a Twitter post that there were more than 500 calls for help.
"Sit tight, we know many of you need help," Hoffman wrote.
The search for loved ones was made more difficult as mobile phone services were often cut.
"A lot of down trees, a lot of flooding everywhere. We are trying to get a hold of my daughter," Terri Byrd said in a vehicle in a Walmart parking lot trying to get mobile service after spending the night at a primary school in Venice.
Across the region, officials and residents spent the morning assessing the damage.
In Punta Gorda, a town directly in the hurricane's path, trees, debris and power lines covered roadways although many buildings remained standing, having withstood the storm's onslaught better than many had feared.
"It was insane," local landscaper Jeffrey Chambers, 53, said, noting the storm brought sideways rains and white out conditions.
"I was like 'Please stop already, just stop.' And it kept going and going."
Ian, now a tropical storm, slackened as it trekked across Florida but was still producing strong winds, heavy rains and storm surge, including in Georgia, South Carolina and North Carolina, the US National Hurricane Center said.
US President Joe Biden spoke to DeSantis on Thursday, saying his administration was committed to continue close co-ordination and that Federal Emergency Management Agency Director Deanne Criswell will be in Florida on Friday.
Biden said that he will travel to the state when conditions allow.
