Spokeswoman Mindy Talmadge says the building on Pier 29 was vacant, but there were some cars parked in the structure when the blaze broke out around 1:50 p.m. Wednesday.
Talmadge says no injuries have been reported. The cause of the fire is under investigation.
Large flames and thick black smoke were coming from the building for part of the afternoon, but by 3:30 p.m. the smoke was mostly white.
Traffic has been stopped along The Embarcadero, which is a main route along the city's waterfront. People are being advised to avoid the area.
San Francisco transit officials say the fire is disrupting transit service in the area.