"I can confirm that we have several fatalities both from the aircraft and within the mobile home the plane crashed into,” Clearwater fire chief Scott Ehlers said in a press briefing.
Mr Ehlers said the pilot was dead and one person on the ground received a minor injury and refused treatment, according to reports from the scene.
The exact number of fatalities from the incident is yet to be confirmed. The number of people on the crashed plane, a single-engine Beechcraft Bonanza V35, is also unclear.
Images posted online by the Clearwater Fire & Rescue Department showed flames that engulfed parts of the park, as smoke billowed from the damaged homes. The pilot had radioed in a Mayday distress call, Mr Ehlers said earlier.
The aircraft crashed into the residential area after the pilot reported an engine failure, a Federal Aviation Administration spokesperson was quoted as saying by CNN.
Frances Yont, a witness to the crash, told CBS affiliate 10 Tampa Bay, that she could feel the heat from the fire when she ran out of her home in Clearwater, roughly 20 miles west of Tampa.
“Everything was popping like propane tanks,” she told the outlet. “We couldn’t do anything,” she said, adding that “it was horrible.”
The authorities confirmed that four homes were damaged in the mobile home park
"A mobile home doesn’t withstand much in the first place, so the aircraft pretty much demolished it. The fire consumed the rest," Mr Ehlers said.
Neighbour Steven Ascari, who posted video of the scene on social media, said first responders arrived quickly and put out the flames within half an hour.
"We heard an explosion outside that shook the entire apartment and next thing you know a giant pillar of smoke was seen," Ascari said.
Clearwater is a city of about 117,000 people on the Gulf Coast about 24 miles (40 km) west of Tampa.
Additional reporting by agencies