As an American art and regional history museum, and the second largest art museum in Georgia, the Columbus Museum offers a diverse collection to the public. The Museum presents visitors from around the world with a comprehensive look at the history of the Chattahoochee River Valley. From clothing and books to furnishings and firearms, the Museum houses over 14,000 artifacts and objects that tell the story of the area's development. The American fine art collection includes paintings, sculptures, and decorative arts from a host of renowned American artists. In addition, the Museum's drawing collection is recognized nationally for its excellence and depth, featured in the 2006 Columbus Museum publication, Lines of Discovery: 225 Years of American Drawings.

In addition to the Museum's collection, the Museum also schedules approximately ten to fifteen temporary exhibitions a year. Regional history, contemporary art, American drawings, watercolors, 19th century cut glass, photography, ceramics, and sculpture are just a few of the many areas in which the Museum has enriched the cultural experiences of visitors.

A range of educational programs, including lectures, films, and art activities attract visitors from all walks of life. The Museum also features Transformations, a hands-on gallery for children.