Rail service to the area began with 17 Mile House station, which opened in 1864 on land deeded by Darius Ogden Mills; it was renamed Millbrae the next year.

South of the Millbrae Avenue bridge, the northbound track splits in two to form a triple-track section to allow passing trains.

[7] The BART platform at Millbrae has six sculptures partially embedded in concrete blocks, with each figure representing a different era in community history.

[8] Forty-two terrazzo benches installed at the station show scenes of local nature and history.

[9][10] In 1862, after buying a section of Rancho Buri Buri from José de la Cruz Sánchez, Darius Ogden Mills deeded land to the under-construction San Francisco and San Jose Railroad in exchange for a station to allow guests to visit his estate.

[2] The station burned again in 1906 and was replaced with a two-story colonnade-style depot of standard SP design the next year.

In 1976, preparing to discontinue the money-losing Peninsula Commute (which instead became publicly funded as Caltrain), the SP proposed to tear down the station.

[12] In August 1980, the building was moved 200 feet (61 m) south to make room for a widening of Millbrae Avenue.

On September 12, 2005, in order to lower these subsidies, BART reduced service so that only the Dublin/Pleasanton line served SFIA and Millbrae stations.

[13] In 2006, Pullman car Civic Center, built in 1941 for the City of San Francisco, was moved adjacent to the station and opened as an exhibit.

[29][13] As built, Millbrae station had four large surface parking lots and a busway on the east side of the tracks.

Construction of a mixed-use transit-oriented development project, Gateway at Millbrae Station, began replacing the surface lots in 2020.

[32] The east surface entrance and elevator were temporarily closed from February 1 to June 6, 2022, with access to the garage maintained directly from the station concourse.

Senate Bill 1029, passed in 2012, provided funds to lengthen the Caltrain platforms for future high-speed rail trains.