The aircraft took off from Boca Raton Airport on its way to Tallahassee, North Florida, and crashed close to Interstate 95 at roughly 10:20 a.m.
As he attempted to escape the wreckage and fire from the collision, a driver was hurt when his vehicle struck a tree.
It is believed that he was transported to the hospital for treatment after suffering non-life-threatening injuries.
The aircraft was identified by the Federal Aviation Administration (FAA) as a Cessna 310 carrying three passengers.
The plane was on fire, according to local media, and firefighters were reacting. Roads close to the scene of the accident were closed.
Investigations have been started by the National Transportation Safety Board (NTSB) and the Federal Aviation Administration (FAA), with the NTSB taking the lead.
