It is situated in the civil parish of São Vicente, in the central part of the municipality of Lisbon, on the northern margin of the Tagus River in the historical district of Alfama.

Meanwhile, in December 1852, the engineer Thomaz Rumball proposed two alternatives, alongside the Museu Militar de Lisboa (Military Museum of Lisbon), or in the proximity of the Largo do Intendente.

[5] The project was designed by Angel Arribas Ugarte, and directed by director João Evangelista de Abreu, and his chief engineer Lecrenier, and constructed by the company Oppermann.

Santa Apolonia became one of several land transport hubs, that included Gare do Oriente, situated 6.5 kilometres (4.0 mi) southwest, Cais do Sodré, Rossio and Entrecampos.

[9] The station is situated along the northern margin of the Tagus River, in the Alfama district of Lisbon, integrated into the urban zone, along the Rua Caminhos de Ferro.

Fronted by Rua Texeira Lopes, the three-register U-shaped building includes a short facade and long parallel wings extending around the rail platforms.