The package was reported on the west side of Steuart Street between Market and Mission streets at 11:23 a.m., according to police.
Streets in the area were shut down, a shelter-in-place order was issued and nearby restaurants evacuated, according to police.
A bomb squad responded to the scene and eventually determined that the package was harmless, according to police.
Police gave San Francisco Municipal Railway officials the all-clear at 3:20 p.m. to resume regular service in the area, Muni spokesman Paul Rose said.
The F-Market/Wharves streetcar line had been switching back near Civic Center, and the 6-Parnassus, 14-Mission, 21-Hayes, and 31-Balboa bus lines were rerouted.