The station opened on December 15, 1846 at the railway line from Berlin's Hamburger Bahnhof to the city of Hamburg. Then the main station in the area, it bore the name Spandau. When in 1871 the parallel railway line from the Lehrter Bahnhof in Berlin to Lehrte opened with a second station west of the Havel river, Spandau received the annex Hamburger Bahnhof to distinguish it from the new station called Lehrter Bahnhof. As both lines were socialised by the Prussian state railways in 1880 and 1884, the former Lehrter Bahnhof was closed for passenger service and remained a freight station. Called Spandau Hauptbahnhof (main station) from 1911 and Berlin-Spandau from 1936, the station was renamed Stresow on 19 May 1997, when the Spandau-West station at the site of the historic Lehrter Bahnhof took over the role.
A S-Bahn station from 1928 on, service was interrupted in 1980 and not resumed until 30 December 1998, when the station reopened in its current form. The entrance building from 1846 is preserved in its original condition and one of the oldest in Germany.