The museum's collection, which includes Jasper Johns, Andy Warhol, Cindy Sherman, Kara Walker, and Alexander Calder, contains historical samples of 1940s–1970s late surrealism, pop art, minimalism, and conceptual art; notable holdings also include 1980s postmodernism, as well as contemporary painting, sculpture, photography, video, installation, and related media.

The current building is known for its signature staircase leading to an elevated ground floor, which has an atrium, the full glass-walled east and west façades giving a direct view of the city and Lake Michigan.

[4] It opened in fall 1967 in a small space at 237 East Ontario Street that had for a time served as the corporate offices of Playboy Enterprises.

[8] The MCA expanded into adjacent buildings to increase gallery space; and in 1977, following a fundraising drive for its 10th anniversary, a three-story neighboring townhouse was purchased, renovated, and connected to the museum.

In his work Circus Or The Caribbean Orange (1978), Matta-Clark made circle cuts in the walls and floors of the townhouse next-door to the first museum.

[12][13] The Board of Trustees then weighed architectural proposals from six finalists: Emilio Ambasz of New York; Tadao Ando of Osaka, Japan; Josef Paul Kleihues of Berlin; Fumihiko Maki of Tokyo; Morphosis of Santa Monica, Calif.; and Christian de Portzamparc of Paris.

The selection process, which started with 209 contenders, was based on professional qualifications, recent projects, and the ability to work closely with the staff of the aspiring museum.

[9] In its first year of operation, the museum hosted the exhibitions, Pictures To Be Read/Poetry To Be Seen, Claes Oldenburg: Projects for Monuments, and Dan Flavin: Pink and Gold, which was the artist's first solo show.

[20] In 1989, the MCA hosted Robert Mapplethorpe, The Perfect Moment, a traveling exhibition organized by the Institute of Contemporary Art in Philadelphia.

Additional 2006 exhibitions featured photographers Catherine Opie and Wolfgang Tillmans as well as Chicago-based cartoonist Chris Ware.

The Turner Prize-winning artist's sound exhibition featured protest songs and drew from Chicago's labor history.

[31] In 2014, the MCA was the only US venue to mount the David Bowie Is... exhibition, which broke previous attendance records for the museum.

[38] Starting in 2002, the MCA began commissioning artists and architects to design and construct public art for the front plaza.

The goal of the program is to link the museum to its neighboring community by extending its programmatic, educational, and outreach functions.

[43] The MCA Stage has featured local, national, and international theater, dance, music, multimedia, and film performances.

[44] Notable MCA Stage appearances include performances by Mikhail Baryshnikov, eighth blackbird, Peter Brook, Marie Chouinard, Merce Cunningham, Philip Glass, Martha Graham, Akram Khan, Taylor Mac, and Twyla Tharp.

[45] In September 2022, the MCA Stage hosted the first annual Chicago Performs, a two-day festival of experimental dance, music, and theater that included admission to the museum and other related programs.

[47] Every spring, MCA presents an annual suite of live, digital, and durational performance works in its On Stage series.

The monumental staircase with projecting bays and plinths that may be used as the base for sculpture is reminiscent of the Propylaia of the Acropolis of Athens.

[54] For its 50th anniversary in 2017, the museum unveiled a $16 million renovation by architects Johnston Marklee, which redesigned 12,000 square feet (1,100 m2) within the existing footprint of the original Joseph Paul Kleihues design.

[56] Complaining that the structure has a more fortress-like exterior than the museum's earlier home, Kamin viewed the architectural attempt as a fumbled work.

[57] Chicago-based architect Douglas Garofalo has described the building as stark, intimidating and "incongruous with contemporary sensibilities".

[39] The interior atrium, which the architect claims links the city to the lake is part of a transcendent space that benefits from the sunlight that enters through the high glass walls.

[58]” In keeping with the museum’s vision of a creative and diverse future, MCA is a leader in collecting works by historically underrepresented artists “with rates more than twice the national average for the work of women (25 percent of acquisitions), four times the national average for Black American artists (almost 10 percent), and seven times the national average for the work of Black American female artists (3.6 percent).”[59] Announced by the Chicago Tribune in June 2011, the MCA initiated the process of reinventing its identity with new curators, a new floor plan, and a new vision.

The main floor's north and south galleries present exhibitions showcasing the museum's permanent collection and work by post-emerging contemporary artists.

[63] During the 2008 fiscal year, the MCA celebrated its 40th anniversary, which inspired gifts of works by artists such as Dan Flavin, Alfredo Jaar, and Thomas Ruff.

Additionally, the museum expanded its collection by acquiring the work of some of the artists it presented during its anniversary celebration such as Carlos Amorales, Tony Oursler, and Adam Pendleton.

The programming includes primary projects and festivals of a broad spectrum of artists presented in performance, discussion, and workshop formats.