Originally known as Lancaster Castle Station in order to distinguish it from the first Lancaster Station (1840–1849), Lancaster station was officially opened on 21 September 1846. The first public service ran into the station on 17 December the same year. The station was built as the southern terminus of the Lancaster and Carlisle Railway after the initial planned route for the line - following the Lancaster Canal and crossing the River Lune from Ladies Walk to Skerton - was changed in favour of a cheaper route west of the city.
The station was remodelled in 1902 when additional lines and platforms were added and further station buildings constructed. The new buildings were styled mock-Elizabethan with the intention of mirroring the battlements of the nearby Lancaster Castle. Platforms 5 and 6 were electrified in 1908 to serve the now-closed Midland Railway route to Morecambe and Heysham. This line closed in January 1966 and the overhead line equipment was removed.
The track layout in the station area was rationalised in 1973 when control of the signalling was transferred to the new Preston Power Signal Box. This included the removal of the track from Platform 6, although this platform had seen no regular use for some time prior to this. The West Coast Main Line through Lancaster was electrified in 1974, and regular electric passenger services recommenced at the station 7 May 1974.