Originally from Ojai, California, Weatherford earned a B.A. in art history and visual arts from Princeton University, and an M.F.A from the Milton Avery School of Fine Arts at Bard College. In 1985, she participated in the Whitney Independent Study Program where she developed her earliest paintings, some of which include colored targets and silkscreened images of flowers, vines, and female figures titled after literary heroines. A profound and longstanding study of nature is reflected in other works from the late 1990s and early 2000s. Weatherford incorporated elements of assemblage into a series of stained canvases, including physical shells, sponges, and starfish. In 2005, Weatherford embarked upon a pivotal series of paintings based on plein-air drawings she made of a sea cave on Pismo Beach, a coastal area a few hours north of Los Angeles.

Her 2012 Bakersfield Project was the first series of paintings to incorporate neon tubing and revealed a new way of making that occupies the artist to this day. The works reflect Weatherford’s previous engagement with gestural forms and immersive scale and are drawn from memory using a variety of techniques and artistic references. The colors and textures of the works indicate shifting lights, atmosphere, and mood, often evoking a specific time, locale, and temperature, such as Greek seafood restaurant murals and liquor store neon signs seen while driving at dusk in Bakersfield, California.