Its collections focus mainly on American art, and its holdings include works by Andrew Wyeth,[1]Jasper Johns (raised in South Carolina), William Henry Johnson, Andy Warhol, Romare Bearden, Jacob Lawrence, Alma Thomas, Helen Turner, Charles Wilson Peale, Eric Fischl, Marylyn Dintenfass, and Leonardo Drew.

The new building is almost 90,000 square feet for spacious exhibition galleries, a museum shop, art storage, a 190-seat auditorium, and classrooms for studio instruction.

[2] In 1985, the Museum refined its collections policy to focus on creating a comprehensive survey of American art using southern related examples.

Among the highlights are a group of pre-Civil War vessels created by African-American potter and poet David Drake, a collection of American Impressionism, and an array of works by 20th-century masters like Georgia O’Keeffe, Romare Bearden, Merton Simpson, and Andy Warhol.

[6] The museum boasts individual works by such twentieth-century masters as George Bellows, Mary Cassatt, Josef Albers, and Philip Guston.

"[7][8] Although Greenville County taxpayers support the museum's operations and building maintenance, no public funds are provided for art purchases.