It is the premier institution devoted to the aesthetic appreciation of folk art and creative expressions of contemporary self-taught artists from the United States and abroad.

In its ongoing exhibitions, educational programming, and outreach, the museum showcases the creative expressions of individuals whose talents developed without formal artistic training.

Despite lacking these institutional fixtures, founding Trustees Joseph B. Martinson and Adele Earnest had a vision: the advancement of the understanding and appreciation of American folk arts.

Offering a more inclusive vision, the museum began to present African American and Latino artworks in their exhibitions and permanent collections.

Director Gerard C. Wertkin announced American folk art's common heritage as “promoting an appreciation of diversity in a way that does not foster ethnic chauvinism or racial division.”[7] The museum further established its broadened outlook with the 1998 formation of the Contemporary Center, a division of the museum devoted to the work of 20th and 21st century self-taught artists, as well as non-American artworks in the tradition of European art brut.

In 2001, the museum opened the Henry Darger Study Center to house 24 of the self-taught artist's works, as well as a collection of his books, tracings, drawings, and source materials.

[9] When MoMA announced that it was going to demolish the building in connection with its expansion, there was outcry and considerable discussion about the issue, but the museum ultimately proceeded with its original plans.

[12] Following the sale, the American Folk Art Museum used its facility at 2 Lincoln Square as its main exhibition and shop space.

Spanning a wide variety of mediums, the collection includes over 1,200 paintings on canvas or panel, 1,500 drawings and works on paper, 1,000 sculptural objects, 1,000 textile items, 200 ceramic objects, 100 pieces of furniture, 300 decorated household items from the Historical Society of Early American Decoration, and two large-scale architectural models.

The collection ranges from early portraits by Sheldon Peck, Ammi Phillips, Asa Ames, colorful paintings by Sam Doyle ,and Samuel Addison Shute and Ruth Whittier Shute, quilts and schoolgirl needlework, furniture, and weathervanes to works by acclaimed masters such as Thornton Dial, Morris Hirshfield, Martín Ramírez, Judith Scott, Mary T. Smith and Bill Traylor.

[16] Additionally, the museum has hosted solo exhibitions dedicated to the work of self-taught greats: Martín Ramírez, Eugene Von Bruenchenhein, Willem van Genk, Ronald Lockett, John Dunkley, Paa Joe, and Bill Traylor.

Subsequent major exhibitions include 2016's Mystery and Benevolence: Masonic and Odd Fellows Folk Art, Securing the Shadow: Posthumous Portraiture in America, Eugen Gabritschevsky: Theater of the Imperceptible, Carlo Zinelli (1916–1974), 2017's War and Pieced: The Annette Gero Collection of Wartime Quilts, 2018's Vestiges & Verse: Notes From the Newfangled Epic, and, also in 2018, Charting the Divine Plan: The Art of Orra White Hitchcock (1796–1863).

At the Self-Taught Genius Gallery in Long Island City, the exhibitions have included Holding Space, Handstitched Worlds: The Cartography of Quilts, and Roadside Attraction.

Featuring more than 100 works of art, "Self-Taught Genius" offered "an intellectually provocative effort to rethink the nature of artistic creativity" from the eighteenth century to the present.

[19] Following its New York premiere, the exhibition travelled to six cities, as part of a national tour funded by the Henry Luce Foundation's 75th anniversary initiative.

Marino Auriti (1891–1980), a self-taught Italian American artist, created the work as an architectural model for imaginary museum that would house all worldly knowledge.