Orange County Fire Authority firefighters responded to the 14000 block of Red Hill Avenue at about 9:15 a.m.
Fire officials said the eucalyptus tree fell onto the vehicle, dwarfing the car underneath and killing the 34-year-old victim inside.
The coroner's office identified the victim as Dennet Bermas of Tustin. Her family members say they called her "Denden."
Family members said she was a nurse at an assisted living facility and was on her way to work when the tragedy happened.
A neighbor told Eyewitness News that he had said "hi" to Bermas just moments before the incident. He said he heard a loud snapping and crashing sound before running over to help.
"I was yelling at her, 'ma'am, ma'am, ma'am' - no response," Danny McCabe said. "I reached in, checked for a pulse and there was none on her wrist. I checked her neck and there was none. I tried to move her head and it was so pinned in that the roof collapsed. I'm sure she died instantly."
The massive tree also took down power lines and crushed part of a carport. Southern California Edison was called to assist with cleanup efforts. Coroner officials were also called to the scene.
The cause of the tree fall is under investigation, but strong winds in the area may be to blame, officials said.
Officials said wind gusts were up to 68 mph in a lot of parts of Orange County.
In another part of Tustin, an 80-year-old woman was injured when a tree snapped in the wind and fell on top of her on her front porch. She is in stable condition and suffered a leg injury, authorities said.
The first major Santa Ana wind event of the season hit Southern California throughout the morning and midday, causing dangerous conditions in several parts of the region. Red flag and high-wind warnings are also in place. Most warnings are set to expire at 8 p.m. Tuesday.
Santa Ana winds: Fierce gusts slam Southern California