Jessie Trefethen was born June 13, 1882 on Peaks Island, Portland, Maine, the daughter of William Henry and Elizabeth Mank Trefethen. She was a ninth generation descendant of the founder of Portland, George Cleves.

She received her A.B. degree in history from Mount Holyoke College in 1907 and then studied art for one year at the Portland School of Art. This was followed by three years study at the Pennsylvania Academy where she was awarded the Cresson Scholarship to support her several study trips to Europe which extended over a number of years.

Miss Trefethen was Head of the Art Department at The Merrill School, Mamaroneck, New York, 1917-1921, and held a similar position at the Knox School in Cooperstown, New York, 1922-1926. In 1926 she accepted the position of Assistant Professor at Oberlin College to replace Eva Oakes as head of the practical art department. She was promoted to Associate Professor in 1945 and retired in 1947 after which she became a professor emeritus.  At Oberlin she taught figure and portrait drawing; line, color and composition; oil and watercolor painting; and the history of modern art. She retired in Portland, Maine.

Outside Oberlin she was best known for her watercolors of the Maine coast, although she did work in Mexico, Nova Scotia, the coast of England and at scenic areas in Lorain County, Ohio. She was admired for the remarkable abstract and rhythmic qualities of her work and her exquisite control over color. After retirement she continued her creative work and had exhibitions at museums in Maine and New York, as well as at the Allen Art Museum until she was over 85 years old.

She died in Portland, Maine on March 9, 1978 at the age of 95.