The blaze was reported before dawn on a sound stage at the film studios, said Los Angeles fire captain Frank Reynoso.
More than 100 city and county firefighters are helping studio staff tackle the flames, which have caused several explosions.
No injuries have been reported at the 230-acre site, which saw filming for King Kong and The War of the Worlds.
Helicopters have been dropping water on to the burning structures, and television pictures showed flames leaping into the air as a thick cloud of smoke covered the site.
What are the implications for artists around the world? Will the loss of this major studio affect the broader company? What response is to be expected from the shareholders?
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