Rubens Peale spent most of his working life managing museums before turning seriously to painting in old age. He directed his father Charles Willson Peale's museum in Philadelphia, helping maintain a business that combined natural-history specimens, portraits, and public instruction. In the early 1820s he took over management of the family's Baltimore museum, continuing its mixture of science, art, and popular exhibition.

In 1825 Peale opened a museum of his own in New York. Competition, changing public tastes, and financial difficulties made the enterprise increasingly hard to sustain. He eventually sold the collection to P. T. Barnum in 1843. By then he had moved to his father-in-law's property near Schuylkill Haven, Pennsylvania, where horticulture and the observation of nature occupied much of his attention. These interests later supplied subjects for a new phase of artistic work.

In 1855, when he was in his seventies, Peale began keeping a journal and devoted himself to still-life painting. Flowers, fruit, and other carefully observed objects connected his pictures with the natural-history interests of his museum career. His daughter Mary Jane, herself an artist, encouraged and instructed him. In his last decade he produced about 130 paintings. Shortly before his death he returned to Philadelphia and studied landscape painting with Edward Moran. He died in 1865. His diaries record this late development alongside a museum career in American collecting and public display.