It is a terminus and located at the northern edge of Venice's historic city (Italian: Centro storico).

Both Santa-Lucia and Mestre stations are managed by Grandi Stazioni and they are connected to each other by Ponte della Libertà (English: Liberty Bridge).

Venice's historic city had access only by river boats or railway until 1933 (construction of the road bridge and of Piazzale Roma).

In order to make room for both the station building and its forecourt, a convent and the Church of Santa Lucia were demolished in 1861.

In addition, certain architectural elements would be recovered and restored; the atrium would be altered to house several retail spaces.

(Platforms 16-23 are situated outside in the redeveloped goods yard directly to the south east of the station) The station is served by the following services: High-speed Domestic Cross-border (D for Germany, A for Austria, F for France, CH for Switzerland, GB for United Kingdom) On 11 December 2016, all ÖBB EuroNight services were rebranded as "Nightjet".

The stop (dock) is called Ferrovia and is served by eight ACTV Vaporetto lines: Media related to Venezia Santa Lucia at Wikimedia Commons