Police received reports of the collision at 4:49 p.m. at Sixth Avenue and Clement Street, Sgt. Michael Andraychak said.
Responding officers found the bicyclist unresponsive, and he was pronounced dead at the scene, Andraychak said.
The Muni vehicle that collided with the bicyclist was a northbound 44-O'Shaughnessy bus, according to officials.
San Francisco Municipal Transportation Agency spokesman Paul Rose said the bus operator will be suspended pending an investigation into the crash.
The bicycle apparently came to a stop under the bus after the collision.
Inbound service on the 44-O'Shaughnessy line was rerouted from Geary Boulevard to Seventh Avenue to California Street after the crash, the SFMTA said.
Outbound service was rerouted from Clement Street to Seventh Avenue to Geary Boulevard.
Inspectors were on the scene as of about 6 p.m.