A civilian male individual suffered a cardiac arrest and died, Los Angeles fire Chief Ralph Terrazas said at a Friday morning news conference.
Crews tried to save his life, but the victim ultimately died at the hospital, according to the Fire Department.
Authorities have not identified that victim, but a resident who lives in the area of the 11000 block of Thunderbird Avenue in Porter Ranch identified him as his neighbor.
The man had been using a garden hose to douse the flames that were approaching his home, the neighbor said.
Video from the scene early Friday shows paramedics wheeling that man into an ambulance.
One firefighter suffered a minor eye injury and was also hospitalized, Terrazas said. No other injuries have been reported.
The blaze has burned more than 11 square miles and was 13% contained as of Friday afternoon. At least 25 homes have been damaged, according to the Fire Department.
Thousands of residents have been asked to leave the area.
"If you remain, we cannot assure your safety," Los Angeles police Chief Michel Moore said on Friday.
More than 1,000 firefighters have been deployed to the "very dynamic" fire, Terrazas said.
Investigators have not determined what ignited the blaze.
Correction: A previous version of this story provided an incorrect number of homes damaged. This post has been updated.