Construction of the South Cove Tunnel and the station shell took place in 1968–1971 in preparation for a rerouting of the Orange Line into the Interstate 95 median.

This gives it several important differences from Chinatown, Downtown Crossing, and State along Washington Street to the north, which were all threaded among existing underground structures.

Because it was easier to dig deeply on the empty plot, Tufts Medical Center station has a subsurface fare mezzanine, rather than having faregates located immediately adjacent to the platforms.

[3] Tufts Medical Center serves both routes (SL4 and SL5) of the Washington Street section of the Silver Line, which operates between downtown and Nubian.

[5][6] At each station between Forest Hills and Tufts Medical Center, two granite columns near the outside entrance have been inscribed with text.

[8][9] However, I-695 was cancelled due to local opposition in 1971; the Elevated remained in service, and the South Cove Tunnel and station sat unused.

[1] Silver Line service on Washington Street between Nubian and Downtown Crossing started on July 20, 2002, replacing the former route 49 bus.

[1][11] The entire Orange Line, including Tufts Medical Center station, was closed from August 19 to September 18, 2022, during maintenance work.