[4] Subsequent expansions included the David Kahler Building in 1975, the Quadracci Pavilion by Spanish architect Santiago Calatrava, inaugurated in 2001, and the East End entrance, opened in 2015.

[13][14] In 1883, local businessman Frederick Layton, a British immigrant who made his fortune through wholesale, meatpacking, and railroad ventures in Wisconsin, suggested establishing an art gallery for the city of Milwaukee.

[20] In 1999, the Milwaukee-based Chipstone Foundation established a partnership with the museum to display part of their collections of American decorative arts and furniture in dedicated galleries on a rotating basis.

[25] The Quadracci Pavilion, a multi-purpose 13,197-square-meter (142,050-square-foot) building including a reception hall, auditorium, exhibition space, and store, was designed by Spanish architect Santiago Calatrava and completed in 2001.

[26] The construction method of concrete slabs into timber frames was revolutionary in architecture, with Windover Hall, a 90-foot (27 m)-tall grand reception area topped with a glass roof, standing at the center of the structure.

The style and symbolism of the building were based on Gothic architecture and designed to represent the shape of a ship looking over Lake Michigan.

As Calatrava stated, “the building’s form is at once formal (completing the composition), functional (controlling the level of light), symbolic (opening to welcome visitors), and iconic (creating a memorable image for the Museum and the city).”[27] The Quadracci Pavilion contains a movable brise soleil that opens up for a wingspan of 217 feet (66 m) during the day, folding at night or during inclement weather.

[30] This was followed in 2010 and 2012 by the acquisition of close to 500 folk and self-taught American artworks from the collections of businessman Anthony Petullo and playwright Lanford Wilson, including paintings and sculpture by African American artists Bill Traylor, Clementine Hunter, William L. Hawkins, Joseph Yoakum, Minnie Evans, and Bessie Harvey.

[33] The expansion was designed by Milwaukee architect James Shields and the HGA firm to provide additional gallery space, including a section devoted to light-based media, photography, and video installations.

[38] The house was built in the High Victorian Gothic style for lawyer and former Wisconsin Supreme Court justice Jason Downer in 1874.

Some artists represented include Gustave Caillebotte, Francisco de Zurbarán, Jean-Honoré Fragonard, Auguste Rodin, Edgar Degas, Claude Monet, Gabriele Münter, Henri de Toulouse-Lautrec, Frank Lloyd Wright, Pablo Picasso, Joan Miró, Wassily Kandinsky, Mark Rothko, Robert Gober, and Andy Warhol.

It also has paintings by European painters Francesco Botticini, Jan Swart van Groningen, Jan van Goyen, Franz von Lenbach, Ferdinand Waldmüller, Carl Spitzweg, William-Adolphe Bouguereau, Jean-Léon Gérôme, Gustave Caillebotte, Camille Pissarro, Jules Bastien-Lepage, and Max Pechstein.

[54] Endowment proceeds cover a fraction of the museum's expenses, leaving it overly dependent on funds from day-to-day operations such as ticket sales.

[57] In June 2015 the museum's display of a work depicting Benedict XVI, composed of 17,000 latex condoms, created outrage among Catholics and others.

[58] The Quadracci Pavilion makes an appearance in the 2008 EA racing video game Need for Speed: Undercover,[59] as well as the film Transformers: Dark of the Moon, where it stands for the headquarters of car collector Dylan Gould (played by actor Patrick Dempsey).