The Williams and Proctor families collected American and European paintings, fine furniture, decorative arts, manuscripts, holographs, rare books and related materials throughout the 19th century and in the early 20th century. Since its founding in 1936, the Museum has sought to enrich and expand these collecting interests.

Highlights of the 19th-century American painting and sculpture collections include works by William M. Chase, Thomas Cole, William Harnett, Winslow Homer, James Peale, Raphaelle Peale, John F. Peto, Hiram Powers, and Augustus Saint-Gaudens.

The Museum's historical American painting collection is noteworthy for works by the Hudson River School, a group of early 19th-century Romantic landscape painters based in New York City who painted views of the Hudson River Valley and surrounding areas. Thomas Cole, a founder of the school, is represented by his famous four-part allegorical series, The Voyage of Life, which he painted in 1839-40. The collection also boasts Hudson River School landscape paintings by Frederic E. Church, Jasper F. Cropsey, Asher B. Durand, Sanford R. Gifford, Henry Inman, George Inness, David Johnson, William T. Richards, Ferdinand Richardt, Francis A. Silva, and Alexander H. Wyant.

The Museum's permanent collection features more than 600 19th-century American drawings, by the best-known artists of the pre-modern era. The drawing collection a significant group of preliminary studies for paintings, as well as works of regional significance by artists who lived and worked in central New York State.

Also included in the Museum collections are Western and Asian graphic arts from the 16th century to the present and 19th-century manuscripts, holographs, watches, rare books, artistic book bindings  collected by the Institute's founders and benefactors.