The incident happened in the 3500 block Valencia Drive around 7:30 p.m., according to the Fullerton Police Department.
Police responded to a report of a car crashing into a house. When they arrived, they found two gunshot victims at the scene.
One was pronounced dead at the scene. The other was transported to a local trauma center and is expected to survive.
A description of a possible suspect and motive was not immediately available.
The exterior of the house was damaged but nobody inside was injured. Police say a possible male suspect was seen running from the area eastbound on Valencia Avenue.
Officers were searching the neighborhood near the scene.
Valencia Drive was closed between Gilbert Street and Magnolia Avenue and the public was asked to avoid the area.