The work of James McGarrell has been exhibited since 1955 at galleries and museums in America and abroad. It has been included in five Whitney Museum Annuals and Biennials, two Carnegie International Exhibitions, Documenta in Kassel Germany and the American Pavilion of the 1968 Venice Biennale. His paintings are in the permanent collections of many institutions including the Metropolitan Museum, the Museum of Modern Art and the Whitney Museum of American Art in New York City; the Hirshhorn Museum and Sculpture Garden in Washington D.C., The Chicago Art Institute, and the art museums of New Orleans, Saint Louis, Santa Barbara, Tulsa, Milwaukee, Hamburg Germany, the Rose Art Museum of Brandeis University and the Pennsylvania Academy in Philadelphia. He has been the recipient of a Guggenheim Fellowship and a Rockefeller Institute Bellagio Residency. In 1995 McGarrell received the Jimmy Ernst Award for lifetime achievement from the American Academy of Arts and Letters and in 2008 the New York Community Trust awarded him The Oscar Williams and Gene Derwood Prize in visual arts.

As the youngest artist included in the controversial 1959 Museum of Modern Art exhibition The New Images of Man, he had been recognized primarily as a post-modern figurative painter. However beginning around 2004 his work has been moving in a direction that neither embraces nor entirely resists imagistic legibility in its radical celebration of the painting act itself.

He has taught at Reed College, Skowhegan, Indiana University and until his retirement from teaching in 1993, at Washington University in St. Louis. That year, while he was serving a term as Artist in Residence at Dartmouth College, he and his wife, the writer and translator Ann McGarrell, moved into the early 19th century house in Newbury Vermont where they now live and work.

He is represented in New York by the ACA Galleries, in Chicago by Printworks and in Washington DC by the Jane Haslem Gallery.