Born in Pennsylvania, Agnes Sims attended the Pennsylvania Academy of Fine Art and the Philadelphia School of Design for Women. Sims later moved to Santa Fe, New Mexico, in the late 1930s, and became a contractor, purchasing and renovating historic houses around Santa Fe. She herself bought a nineteenth-century house on Canyon Road and built a compound including a house for herself and one for her long-time partner, Mary Louis Aswell. Sims was introduced to the Galisteo Basin south of Santa Fe which was dotted with the ruins of prehistoric Indian Pueblos, and home to tens of thousands of ancient petroglyphs. The rock art captivated Sims and became her primary inspiration for the rest of her career. She recorded 3000 petroglyphs in drawings and thousands in photographs. In 1949 Sims was given a grant to further her research, and in 1950, published a portfolio of selected rock drawings titled, San Cristobal Petroglyphs.
Unlike Sims documentary drawings of petroglyphs, her paintings and sculpture were never literal copies, rather adaptations of two-dimensional people and animal transformed in to art that fit into the larger world of mid-century modernism. She used simple, idiosyncratic figures to create her own symbolism, the original meaning of the ancient art being lost to the past.
Sims is known for her paintings and sculptures inspired by prehistoric rock art of New Mexico and worked in a wide array of media. Her oil paintings on canvas often were mixed with an earthen medium which gave them a rough , stone-like texture. She developed a batik-like resist process for painting on cloth and used it to produce large, un-stretched wall hangings. Sims was a prolific sculptor, working in wood, stone, bronze, terra-cotta, fiberglass and polyester. Sims was given one woman shows at the Brooklyn Museum, U.S. Embassy in London, and the Museum of Fine Art in Santa Fe.