The museum has its origins in the art and natural history cabinet of Duke Charles I of Brunswick, which he opened in 1754 at the suggestion of the Dutch physician Daniel de Superville.

The museum houses an important collection of Western old master paintings, and is especially strong in Northern European art since the Renaissance, including works by Cranach (a very strong collection), Holbein, Dürer, Van Dyck, Rubens, and Rembrandt.

The museum is based on the Schloss Salzdahlum art collection of Anthony Ulrich, Duke of Brunswick-Lüneburg (1633–1714), after whom it is named.

Among the manuscript items is the journal of Matthäus Schwarz, an accountant very interested in fashion who documented his outfits throughout his adult life at a time when it was thought that people not of the highest rank dressed drably.

As a result of this research, a painting by Rombout van Troyen, "Felsgrotte mit Opferszene" was restituted to the heirs of the Jewish physician Hans Herxheimer from Frankfurt am Main (Frankfurt 1880-1944 Theresienstadt) and a painting by Max Joseph Wagenbauer, "Großes Bauerngehöft am Dorfrand" (Great Farm with a Village in the far Distance) was the object of a financial settlement.