Ōkubo station opened on 5 May 1895 as part of the Kinoe railway with both passenger and freight rail services.

On 1 October 1906, the station and all trains serving were nationalised into Japanese National Railways (JNR).

Upon the privatisation of JNR on 1 April 1989, Ōkubo station became part of JR East, which comprises all trains serving the eastern and northern sections of Honshu.

Beginning in November 2001, the Suica RFID-based electronic ticketing system has been accepted at Ōkubo station.

Specifically, the station lies to the south of Ōkubo Street (大久保通り, Ōkubo-dōri) and west of the Yamanote Line-enclosed city centre, making it the first stop westbound outside of central Tokyo.