In 1888, when Frederick Layton built an art gallery near Cathedral Square, other civic-minded individuals formed the Milwaukee Art Association (later Milwaukee Art Institute). In 1957, the Layton Art Gallery moved the Layton collection, together with the Milwaukee Art Institute, into the Eero Saarinen–designed War Memorial Center. From this beginning, the Milwaukee Art Center started to grow. A building addition in 1975 by David Kahler provided more gallery space for the expanding Collection, and in 2001, architect Santiago Calatrava designed the Quadracci Pavilion, which not only provided what was now the Milwaukee Art Museum with greater public gathering space, but also gave the city of Milwaukee a new, international icon.

In the late 1960s, Mrs. Harry (Peg) Lynde Bradley offered her entire collection of more than six hundred Modern works of art to the Museum. She challenged the community to build an addition to house her extensive collection and donated $1 million towards construction. The challenge was met: in 1975, the Kahler building opened with vastly enlarged galleries for the Museum. This decade saw a number of important gifts to the Collection, including the Richard and Erna Flagg Collection and the René von Schleinitz Collection. The Museum’s Friends of Arts started the popular Bal du Lac (1958) and Lakefront Festival of Arts (1963), raising additional funds for Collection growth.

In 1980, the Milwaukee Art Center changed its name to the Milwaukee Art Museum and, in 1983, was accredited by the American Association of Museums.

In 1988 the Museum celebrated its centennial and, looking towards the future, developed plans for another expansion. On December 10, 1997, the Milwaukee Art Museum began construction on the addition Spanish architect Santiago Calatrava designed to carry the Museum into the next millennium. The bold Quadracci Pavilion opened in 2001 to rave reviews and was adopted as an icon of Milwaukee. The project included a grand hall, new exhibition galleries, and an auditorium, as well as a store and a café, bringing the total size of the Museum to 341,000 square feet.