United States President Donald Trump has declared a state of emergency for the region.
Hurricane Michael has killed one person in northern Florida - the first confirmed death from the powerful storm.
There is "one hurricane-related fatality," Olivia Smith, public information officer for the Gadsden County Board of County Commissioners, said.
She said the incident was "debris-related. There was a tree involved".
She could not say what time the death occurred or give any details about the victim.
Smith said the situation was dangerous even for emergency personnel.
"We've been very cautious with sending our first responders out right now," she said, after Michael made landfall as a raging Category 4 hurricane that toppled trees and power lines.
Hurricane Michael earlier made landfall just northwest of Mexico Beach, Florida.
Powerful winds, devastating storm surge and heavy rain are predicted in the Florida Panhandle, the finger-shaped strip of land along the Gulf of Mexico.
"Hurricane Michael is forecast to be the most destructive storm to hit the Florida Panhandle in a century," Governor Rick Scott said.
"Along our coast, communities are going to see unimaginable devastation.
"The National Hurricane Center is expecting storm surge to be between nine and 2.7-3.6 meters.
"Water will come miles in shore and could easily rise over the roofs of houses."
Hundreds of thousands of people were ordered to evacuate their homes and the governor told residents that if they have not already done so it was now too late.
"The time to evacuate the coastal areas has come and gone... Hunker down, and be careful," he said. "Don't go out in the middle of this. You are not going to survive it. It's deadly."
At 11.00 am Eastern time (0200 AEDT), Michael was about 95 kms south-southwest of Panama City and moving north-northeast at 22km/h, the NHC said.
"This is, unfortunately, a historical and incredibly dangerous and life-threatening situation," NHC director Ken Graham said. "It's going to be incredibly catastrophic."
Brock Long, the head of the Federal Emergency Management Agency (FEMA), said many Florida buildings were not built to withstand a storm above the strength of a Category 3 hurricane.
"We're going to see a lot of wind damage," Long said, and some residents could expect not to have power restored for weeks.
"This is the final call for anybody that needs to get out," he said. "Those who stick around to experience storm surge don't typically live to tell about it unfortunately."
Residents of the neighboring state of Georgia should also expect to be heavily impacted by the storm, the FEMA head said. "Citizens in Georgia need to wake up and pay attention," Long said.
Mike Thomas, the mayor of Panama City Beach, a resort west of Panama City, said he expected there would be casualties and that emergency personnel would not go out when winds get over 80km/h.
"It's going to be horrible," Thomas told CNN. "We're going to get some people hurt."
An estimated 375,000 people in more than 20 counties were ordered or advised to evacuate.
The National Weather Service office in the state capital Tallahassee issued a dramatic appeal for people to comply with evacuation orders.
"Hurricane Michael is an unprecedented event and cannot be compared to any of our previous events. Do not risk your life, leave NOW if you were told to do so," it said.
The NWS said it had found no record of any previous Category 4 hurricanes that made landfall in the Panhandle or the "Big Bend" coastal region.
"This situation has NEVER happened before," it said on Twitter.
President Donald Trump issued an emergency declaration for Florida, freeing up federal funds for relief operations and providing the assistance of FEMA, which has more than 3,000 people on the ground.
State officials issued disaster declarations in Alabama and Georgia and the storm is also expected to bring heavy rainfall to North and South Carolina.
The Carolinas are still recovering from Hurricane Florence, which left dozens dead and is estimated to have caused billions of dollars in damage last month.
It made landfall on the coast as a Category 1 hurricane on September 14 and drenched some parts of the state with 101 centimeters of rain.
Last year saw a string of catastrophic storms batter the western Atlantic - including Irma, Maria and Harvey, which caused a record-equaling $125 billion (USD) in damage when it flooded the Houston metropolitan area.
Scientists have long warned that global warming will make storms more destructive, and some say the evidence for this may already be visible.
Five deadliest hurricanes
Following is a list of the world’s five most deadly hurricanes. Hurricanes form over the Atlantic and North Pacific oceans and cause most damage to the Americas while typhoons form in the Northwest Pacific Ocean, impacting Asia.
1. The Great Hurricane, Caribbean, 1780 - Death toll 20,000
The deadliest hurricane on record cost the lives of about 20,000 people, with most of the damage and fatalities occurring in Barbados and surrounding islands. Predating modern meteorological technology, the formation point and exact wind strengths of the hurricane are unknown.
2. Hurricane Mitch, Central America, 1998 - Death toll 19,000
Hurricane Mitch reportedly killed about 19,000 people. Classified as a Category 5 - the highest ranking on the Saffir-Simpson scale - the greatest number of fatalities was in Honduras where severe rainfall led to mud slides and flooding.
3. Galveston Hurricane, Texas, 1900 - Death toll between 6,000-12,000
The Galveston Hurricane caused the greatest number of deaths on the US mainland. Ranked as a Category 4, the disaster ruined the town’s commercial industry and its status as a major port whilst claiming the lives of up to 12,000 inhabitants.
4. Hurricane Fifi, Honduras, 1974 - Death toll 8,000-10,000
Hurricane Fifi is the lowest measured hurricane included on this list but it proved to be deadly and destructive for the island of Honduras. The name Fifi was removed from the rotating list of hurricane names due to high number of fatalities.
5. Dominican Republic Hurricane, Caribbean, 1930 - Death toll 2,000-8,000
Characterized by strong winds and heavy rainfall, the hurricane of 1930 caused severe damage to the Dominican Republic. The island struggled to provide effective and quick relief to its citizens and for its infrastructure.
Sources; National Ocean Service, World Heritage Encyclopaedia, National Hurricane Centre