Her travels began in 1928, after her father died. She spend 1928 and 1929 living and working in Samoa, then spent another two years in Europe before resettling in San Diego in 1932, where she married her childhood friend, sculptor Donal Hord. Separating from Hord, she moved to Los Angeles in 1934, joining the post-surrealist group around Lorser Feitelson and Helen Lundeberg, and participating in the mural division of the Federal Arts Project, where she learned the art of screenprinting, which would become her favored graphic technique. She returned to San Francisco in 1942. She traveled to Paris in 1949/51, to Africa in 1966/67, to England, France and Holland in 1970, to Bali, Java and Sumatra in 1974, and to China and Japan in 1982/85.
In 1968, in collaboration with Marlys Mayfield, she co-wrote Notan:The Dark-Light Principle of Design. The book was republished in 1991 and has been translated into many languages.
Bothwell received many honors in her lifetime, including an Abraham Rosenberg Fellowship, the 1979 San Francisco Women in the Arts Award and two Pollock-Krasner grants for 1998-2000. Her art is in the collections of museums throughout the world, including the Metropolitan Museum of Art, Museum of Modern Art, the Whitney Museum of American Art, the Bibliotheque Nationale in Paris, the Victoria & Albert Museum in London and the Hunterian Museum and Art Gallery, Glasgow, Scotland.
She taught at the San Francisco Art Institute, the Mendocino Art Center, the Parsons School of Design in New York, the Ansel Adams Photography Workshops in Yosemite and the Victor School of Photography in Colorado.