Born in Alabama, Goldthwaite studied art at the Naitonal Academy of Design in New York, before moving to Paris in 1906. She go to know Gertrude Stein and her circle of modern artists, including Matisse and Picasso and became part of a small group of young artists who received criticism from Charles Guerin, a follower of Cezanne. She returned to the US and exhibited in the Armory Show of 1913, which introduced European modern styles to many Americans.
After 1915 she split her time between New York and Alabama, where she became an important regional artist, known for her scenes of the American South. In New York she taught at the Art Students League and exhibited at Edith Halpert's Downtown Gallery.
Goldthwaite was also a crusader for women's rights and equal rights.
Her work is many major museums including the Metropolitan Museum of Art, Smithsonian American Art Museum, and the Cleveland Museum of Art.
