The station building was fairly small in size and inconveniently located some distance from the Berlin city centre, south of the Landwehrkanal.

The surrounding area in the Tempelhofer Vorstadt quarter (today part of the Kreuzberg district) was largely dominated by railway infrastructure.

Trains ran to the Berliner Bahnhof in Dresden's Friedrichstadt quarter, about 174 km (108 mi) in the south, with through coaches to Prague and Vienna.

It took on all long-distance services, and it was largely through this that it became known as Berlin's "Gateway to the South," its trains ultimately reaching Rome, Naples and Athens.

Its original route, opened in stages during 1902, comprised a through section from Warschauer Brücke to Knie, with a triangular junction between Möckernbrücke and Bülowstraße giving access to Potsdamer Platz.