In 1920, the Nierendorf brothers, Karl Nierendorf (April 18, 1889–October 25,1947) and Josef Nierendorf (August 19, 1898–June 21, 1949), founded the gallery Nierendorf Köln Neue Kunst in Cologne, participating in the art trade and organizing exhibitions.

Karl Nierendorf took over the Graphische Kabinett of J. B. Neumann in Berlin in 1923.

In 1925, Josef Nierendorf relocated the gallery for one year from Cologne to Düsseldorf. Karl Nierendorf established the gallery Neumann-Nierendorf GmbH in Berlin, and managed the gallery from 1926 to 1933 under this name, together with his brother Josef.

In September 1933, the renaming of the gallery, to Galerie Nierendorf GmbH, took place.

In May 1936, Karl Nierendorf traveled to the United States and set up the Nierendorf gallery in New York in 1937, while Josef Nierendorf managed the gallery in Berlin by himself.

Josef Nierendorf organized exhibitions until the summer of 1938. Karl Nierendorf organized exhibitions with German artists in New York.

In 1939, Josef Nierendorf stored the stocks of the Berlin gallery in a small shop. At the outbreak of World War II, he was called up to the Wehrmacht, and therefore canceled the registration of his business. Karl Nierendorf managed his gallery in New York until 1946 with increasing success and acquired American citizenship.

Karl Nierendorf traveled to Germany and other European countries from May 1946 to September 1947, while his gallery was run by his employees.

Karl Nierendorf died in 1947 without making a last will and testament, and because there were only German heirs, his gallery was closed, and his estate was confiscated by the state of New York.

In January 1948, the Guggenheim Museum bought the Estate of Karl Nierendorf for US$72,000, including more than 150 works of art by Paul Klee. The German heirs did not receive anything, because the proceeds were balanced with liabilities and administrative costs.

In 1949, Josef Nierendorf intended to start again with the art trade in one of the rooms of the bookshop of his wife in Berlin, but he died on June 21, 1949.

Florian Karsch, the stepson of Josef Nierendorf set up Galerie Meta Nierendorf in 1955, under the name of his mother, together with Inge Loewe, his future wife. Following in the footsteps of Josef Nierendorf, he started to trade in works of art, and to organize exhibitions on a regular basis in a small room of the bookstore.

In 1963, Florian Karsch, the manager of the gallery, rented new rooms in the house of Hardenbergstraße 19, and registered the company under the name Galerie Nierendorf. The gallery has been located in this house ever since. 

Since 2011, Ergün Özdemir-Karsch, the son of Florian Karsch, has owned the gallery.