The street was the location of the SS Reich Security Main Office (RSHA), the headquarters of the Sicherheitspolizei, SD, Einsatzgruppen and Gestapo.

Niederkirchnerstraße is also the site of the Martin-Gropius-Bau exhibition hall, built in 1881 by Martin Gropius and Heino Schmieden as a Museum of Decorative Arts, and the Abgeordnetenhaus von Berlin, from 1899 until 1933 seat of the Preußischer Landtag, the second chamber of the Prussian parliament.

It formed the nucleus of the complex of buildings including the neighbouring Hotel Prinz Albrecht on Prinz-Albrecht-Straße 9 and the Prinz-Albrecht-Palais itself, which was taken over by the Sicherheitsdienst (SD) under Reinhard Heydrich in 1934.

Himmler himself operated out of the building from an office on the top floor, thus making #8 Prince Albrecht Street the default headquarters for the entire SS.

After World War II, in 1951, the authorities of East Berlin renamed Prinz-Albrecht-Straße to Niederkirchnerstraße in honour of Käthe Niederkirchner (1909–1944), a member of the communist resistance to the Nazis.