A painter of landscapes, portraits, and genre pictures, Gladys Nelson Smith was raised on a farm near Chelsea, Kansas. She began to draw at an early age and in 1912 matriculated at the University of Kansas, where she majored in fine art. In 1918 she married a fellow classmate and followed him to various locations. In 1924 the couple settled in Washington, D.C., and Smith refined her skills at the Corcoran School of Art.
Although Smith spent her early life in the mid-west, she came to artistic maturity in the nation's capital, and her paintings are strongly identified with its life and landscape. In the 1920s she was chiefly admired for her paintings of children. In the 1930s she recorded the quaint charms of Georgetown and other local scenery. In 1936 the Smiths bought an 86-acre farm in Frederick County, Maryland, which became their weekend retreat. It was used in many of Smith's subsequent landscapes.
An avid gardener, Smith had a particular interest in flowers and became known in the 1940s for her floral still lifes, often studied in her own garden.