Erna Gunther was born in Brooklyn, New York, in 1896. She graduated from Barnard College in 1919 and immediately started graduate study at Columbia University in anthropology. She received her Master's degree in 1920 under the tutelage of Franz Boas, who is generally credited with being the "father of American anthropology." Leslie Spier, her husband, received an appointment as the University of Washington's resident anthropologist, and the couple moved to Seattle. She joined the University of Washington faculty in 1923, and during the next four years produced several major publications on Northwest Coast Indians. Spier left the University of Washington to accept a position at the University of Oklahoma, and Gunther returned to Columbia University to receive her Ph.D., but both returned to Seattle in 1929. The marriage floundered, and Spier left in 1930. Gunther remained at the University of Washington to become the director of the museum (later called the Burke Museum), and as chairman of the Anthropology Department.

The department consisted of two faculty members, Melville Jacobs and herself. The challenge of keeping the department alive and growing was prodigious in a university atmosphere often hostile to both anthropology and female faculty. Realizing that local public support counted as much as a reputation for scholarship, she devoted a great deal of energy speaking to Cub Scout packs, business groups, women's clubs, church assemblies, and other civic associations. During the 1950's Gunther served on the Advisory Board on Historic Sites to the Washington Statae Parks and Recreation Comission, identifying and evaluating sites for preservation and development. She also promoted the appreciation of Indian culture through a radio series, and later a television program, entitled "Museum Chat." Her strategy succeeded; by the time she resigned as department chair in 1955, there were ten full-time faculty. The Museum flourished likewise under her direction. Facing mandatory retirement, she left the University of Washington in 1966 to join the the Department of Anthropology and Geography at the University of Alaska, Fairbanks for three years.

She returned to Seattle and began an active retirement. Her expertise in setting up museum exhibits and reorganizing collections remained much in demand, leading to her traveling extensively. In 1971, she received the Robert Gray Medal, the highest award of the Washington State Historical Society, in honor of her many career achievements. She published her last important original work, , in 1972.

During her career, she was instrumental in opening the eyes of both the public and the scholarly community to the importance of Northwest Coast Indian culture. Following the lead of Boas, her scholarship insisted on understanding Native American culture on its own terms by drawing on ethnography, history and archaeology. The exhibit she assembled at the 1939 San Francisco International Exposition introduced Northwest Indian art to the general public, and sparked a revival of interest in the region's great woodcarvers. Her arrangement of Indian art for the 1962 World's Fair in Seattle was wildly popular and earned her tremendous praise. She was a passionate supporter of Native American civil rights, and in the 1950s participated in the founding of the Congress of American Indians.

Erna Gunther died in 1982.