Leipziger Straße has existed along this line since about the Baroque Friedrichstadt extension, laid out in 1688 at the behest of Elector Frederick III of Brandenburg.

Near the eastern end, Leipziger Straße traversed Dönhoffplatz [de], named after Prussian general lieutenant Alexander von Dönhoff (1683–1742), where an obelisk marked the zero point of the mileage on the road to Potsdam.

Prime minister Karl August von Hardenberg (1750–1822) had a city palais built here, which from 1848 served as seat of the Prussian Landtag.

The church was heavily damaged by Allied bombing in World War II and its ruins were demolished by the Senate of West Berlin in March 1961 to build the Axel Springer AG headquarters.

The area around the Wilhelmstraße intersection before World War II was one of the centres of German national administration, being the location of various governmental buildings.

Despite the low traffic volume, the eastern half of the road between Spittelmarkt and Charlottenstraße from 1969 onwards was broadened and rebuilt as a prestigious street of a Socialist capital with four car lanes in each direction, a median and broad pavements including an underpass for pedestrians.

Dönhoffplatz was rebuilt as a green area and decorated with the reconstructed 18th century colonnades by Carl von Gontard, installed roughly at the historic site.