The museum, housed in a 13th-century Dominican religious sisters' convent and a 1906 former public baths building, is home to the Isenheim Altarpiece by the German Renaissance painter Matthias Grünewald and features a large collection of local and international artworks and manufactured artifacts from prehistorical to contemporary times.

The collection at first centered around a Roman mosaic found in Bergheim, Haut-Rhin, still displayed today, and plaster copies of antique sculptures on loan from the Louvre.

[5] In the 1950s, and again in the 1980s, the need appeared for the museum, which had seen a steady growth of the number of its displayed artefacts in every domain, to gain more space by using available surface more appropriately, and was each time addressed as far as the classified character of the building in itself could allow.

Other sections displayed by the museum are : local and international archeology; medieval, Renaissance and baroque sculpture (religious as well as profane) and stained glass; weapons, furniture, music instruments and toys from the 14th to the 19th century; ancient, ornate wine barrels (a collection donated by Jean-Jacques Waltz in 1927); modern and contemporary art.

[5] Because of a general lack of space, this last collection, although very well furnished (works by Pablo Picasso, Jean Dubuffet, Fernand Léger, Serge Poliakoff, Georges Rouault, Pierre Bonnard, Robert Delaunay, Otto Dix, Maria Helena Vieira da Silva and others) had only seldom been displayed in its entirety.