42nd Street station was built on August 26, 1878, by the New York Elevated Railway Company, and was the penultimate station on the Third Avenue El until it was expanded to 67th Street almost a month later.

In 1904, Interborough Rapid Transit opened the Grand Central Subway station, which gained platforms for the IRT Flushing Line in 1915, and new platforms for the expanded IRT Lexington Avenue Line in 1918, the same year the original platforms at the station were converted for the 42nd Street Shuttle.

By this time, the shuttle became obsolete and after the Grand Central El station was closed on December 6, 1923, the shuttle platform at 42nd Street was closed on December 23, 1923.

When the IRT Second Avenue Line was closed on June 13, 1942, a free transfer for Third Avenue Line passengers was made available to and from the subway services at Grand Central–42nd Street to replace the direct service to lower Manhattan that was lost.

The station closed entirely on May 12, 1955, with the ending of all service on the Third Avenue El south of 149th Street.