Due to its north-southerly direction, it forms important junctions with the east-western axes, most notably with Leipziger Straße and Unter den Linden.

As central Berlin's traditional shopping street, Friedrichstraße is three blocks east of the parallel Wilhelmstraße, the historic heart of the old government quarter (German: Regierungsviertel) until 1945.

The section in West Berlin was partly rebuilt as a residential street; in the late 1960s, the remains of the former Belle-Alliance-Platz at the end of the Friedrichstraße, renamed Mehringplatz, were completely demolished and replaced with a concrete housing and office development designed by Hans Scharoun.

[5] Philip Johnson created parts of the American Business Center at Checkpoint Charlie, a $751 million five-building complex of offices, shops and apartments developed by Ronald Lauder and Central European Media Enterprises.

In 2020, a section of Friedrichstraße was closed off for motorized traffic during a five-month trial period with the intent to revitalize urban space.