Santa Fe closed the station for passenger service in 1966 and completely shuttered the building in the early 1990s.

When passenger service to Fresno was reinstated on March 5, 1974, Amtrak used a space in the nearby freight house.

The station reopened on February 12, 2005, after a US$6 million renovation project largely restored it to its original 1899 appearance.

From its beginning until Amtrak took over nearly all passenger rail service within the United States in 1971, the station was served by ATSF trains, including the famous San Francisco Chief and the Oakland-Barstow line.

[12] Excluding passengers who are transferring to a Thruway Bus, Fresno has the highest ridership on the San Joaquins service.

[2] The Santa Fe passenger depot has two tracks, but only one side platform sees regular service.