The station opened on October 23, 1932 as a one-station extension of the Boylston Street subway to relieve congestion in the square.

The Kenmore Loop connects the outer tracks, allowing inbound C and D trains to reverse direction without entering the main subway.

Streetcar passengers would make a cross-platform transfer to subway trains, similar to the then-recently-opened Ashmont station.

The streetcar tracks were placed on a wooden structure in the station and at the surface incline pending the future tunnel extension.

[15][16] Buses originally stopped at the curb, which required them to cut across multiple lanes of traffic to loop from inbound to outbound.

In early 1939, the Chamber of Commerce proposed a busway in the center of the square, with direct access to the station mezzanine below.

[28][29] The station was closed for two months in 1996, after the Muddy River overflowed its banks, completely submerging the platform and some of the mezzanine.

[30][31] During the closure, substitute service was provided by commuter rail trains between Riverside and South Station.

[35] Separately, the south entrance to the station was moved inside the Boston University-funded Hotel Commonwealth during its 2002-03 construction.

[39][34]: 31  The project also involved streetscape improvements with trees and brick sidewalks, intended to make Kenmore Square resemble Beacon Hill and the Back Bay as a break from its rough reputation.

[39] Previously undocumented utilities delayed excavation, and keeping the station open during construction presented difficulties.

[34]: 8, 30  Art panels featuring Red Sox players on station signs were unveiled at a ribbon-cutting ceremony on April 22, 2010.