Two of the teens died and the other two were treated at a nearby hospital after shots were fired at Libby Lake Park around 9 p.m. PDT.
The victims were described as three males and a female. There was no immediate indication they were connected to any local street gangs.
The gunmen were believed to be driving a gray or silver Toyota truck seen leaving the area, police said.
Witnesses told KNSD-TV in San Diego they saw several people running from the park shortly after the shots were fired.
The park is located in a relatively quiet residential neighborhood; however, about two years ago, two teenage boys were shot dead not far from the scene of Wednesday's slayings.