The retired Endeavour, the youngest shuttle of the agency's fleet, is to be delivered to the museum next year, SPACE.com reported.
Los Angeles mayor Antonio Villaraigosa signed the title transfer Tuesday at a ceremony at the museum.
"NASA is pleased to share this wonderful orbiter with the California Science Center to help inspire a new generation of explorers," NASA chief Charles Bolden said in a statement. "The next chapter in space exploration begins now, and we're standing on the shoulders of the men and women of the shuttle program to reach farther into the solar system."
The California Science Center is one of four locations across the country selected by Bolden to display NASA's retired space shuttle vehicles.
Endeavour's sister ship Atlantis will be displayed at the Kennedy Space Center Visitor Complex in Florida, while Discovery, the oldest shuttle that flew the most missions, will be sent to the Smithsonian Institution's National Air and Space Museum in Washington, D.C.
NASA's Enterprise prototype shuttle, which was used for testing but never flew in space, will go to New York City to be displayed at the Intrepid Sea, Air & Space Museum.