The partial collapse was reported just after 7:45 a.m. at one of the World War II-era blimp hangars on the grounds of the former Marine Corps Air Station, said Capt. Steve Concialdi of the Orange County Fire Authority.
"There's a giant hole in the roof," he said.
Hazardous-material crews were called to stop the helium leak.
The cause of the collapse was not known, but debris was believed to have fallen on the experimental airship, which is more than 200 feet long.
The dirigible is being developed by Worldwide Aeros, which says it will be capable of carrying 66 tons of cargo.
The extent of damage to the vessel is not known. No injuries were reported.
The Department of Defense and NASA have invested $35 million in the prototype because of its potential to one day carry more cargo than any other aircraft to disaster zones and military bases.
The company says the cargo airship's potential to carry more cargo more efficiently than ever before would provide the U.S. military with an advantage on the battlefield and greater capacity to save more lives during natural disasters.
The lighter-than-air vehicle is not a blimp because it has a rigid structure made out of ultra-light carbon fiber and aluminum underneath its high-tech Mylar skin. Inside, balloons hold the helium that gives the vehicle lift. Unlike hydrogen, the gas used in the Hindenburg airship that crashed in 1937, helium is not flammable.
The airship can take off vertically, like a helicopter, then change its buoyancy to become heavier than air for landing and unloading.
A call to a spokesperson for Worldwide Aeros was not immediately returned.