Established in 1991, Catharine Clark Gallery exhibits the work of contemporary artists working across a wide range of media. The gallery has pioneered the presentation of new media art in San Francisco and is the first commercial gallery in the area with a dedicated media room. Exhibitions are hosted on a six week schedule and generally feature solo artist presentations in conjunction with media room installations.

The gallery's program has garnered critical attention from numerous publications, including the New York Times, Artforum, Flash Art, Tema Celeste, Art in America, ARTnews, Modern Painters, and Art Review. Gallery artists have exhibited at international venues and institutions such as the Museum of Modern Art, the Whitney Museum of American Art, the Metropolitan Museum of Art, the San Francisco Museum of Modern Art, the de Young Museum, the Serpentine Gallery, the Smithsonian American Art Museum, the Queensland Art Gallery, the Contemporary Art Museum in Houston, the Stadt Reutlingen Museum in Germany, and Manifesta 11.

In 2010, Catharine Clark Gallery opened a satellite space in a residential apartment in New York’s Chelsea neighborhood, which hosts exhibits, performances and installations of gallery artists’ work several times a year. In September 2013, the gallery moved to a newly renovated space in San Francisco's Potrero Hill neighborhood. Housed in a former door factory, the space was redesigned by Los Angeles-based architect Tim Campbell.

Located within San Francisco's emerging DoReMi arts district (comprised of adjoining neighborhoods Dogpatch, Potrero Hill, and the Mission), Catharine Clark Gallery is situated in proximity to leading arts venues such as California College of the Arts (CCA), the CCA Wattis Institute for Contemporary Arts, the Museum of Craft and Design and Minnesota Street Project, as well as several contemporary fine art galleries.