The crash occurred last evening in Newport Beach, on Jamboree Road near Island Lagoon Drive, according to Newport Beach Police Department spokeswoman Kathy Lowe.
She said the car, an Infiniti, had been heading south on Jamboree Road in the direction of Pacific Coast Highway when it veered off the road and into the center divider. It struck the tree, ripped apart and burst into flames.
Four people were ejected from the vehicle, and another passenger was partly ejected, police said.
The other was taken to the trauma center at Mission Hospital Regional Medical Center in Mission Viejo but could not be resuscitated, according to Lowe.
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"This is such a tragic accident when you have one car and all five occupants are deceased," Lowe said.
Police said they were still investigating and could not say what caused the accident.
Late last evening, debris, including twisted hunks of metal, stretched for several blocks around the crash site.
Lowe called it the worst accident "in recent memory" in Newport Beach.
In June 2011, three people died in a 10-vehicle crash on Mariners Mile, including a former Corona del Mar High School track star.