Pope.L studied at Pratt Institute before receiving his BA from Montclair State College (1978). He then attended the Independent Study Program at the Whitney Museum of American Art before earning his MFA at Rutgers, the State University of New Jersey in 1981.

His solo exhibitions include William Pope.L: Trinket, Museum of Contemporary Art, Los Angeles (2015); Cage Unrequited, Soto Vélez Cultural and Educational Center, Performa, NY (2013); Reenactor, Williams Center Gallery at Lafayette College, Easton, PA (2012); landscape+object+animal, Mitchell-Innes & Nash, New York (2010); Color Isn’t Matter, Samson Projects, Boston (2010); The Black Factory, Art Projects, Art Basel Miami Beach (2009); Corbu Pops, Carpenter Center for the Visual Arts, Harvard University, Cambridge, MA (2009); Drawing, Dreaming, Drowning, Art Institute of Chicago (2008); Art After White People: Time, Trees, and Celluloid . . . , Santa Monica Museum of Art, Santa Monica, CA (2007); William Pope.L: The Black Factory and Other Good Works, Yerba Buena Center for the Arts, San Francisco (2007); eRacism: Retrospective Exhibition, Institute of Contemporary Art at Maine College of Art, Portland (2002); eRacism: White Room, Thread Waxing Space, New York (2000); and Eating the Wall Street Journal and Other Current Consumptions, Mobius, Boston (2000). His performances include The Black Factory national tour (2004–5); Community Crawls, select venues (2000–2005); The Great White Way: 22 Miles, 5 Years, 1 Street, Whitney Biennial, Whitney Museum of American Art, New York (2002) and elsewhere (2001–2); and Eating the Wall Street Journal, Mobius, Boston and SculptureCenter, New York (2000).

His group exhibitions include Against the Grain: Wood in Contemporary Craft and Design, Museum of Art and Design, New York (2013); superhuman, Central Utah Art Center, Ephraim (2012); The Last Newspaper, New Museum of Contemporary Art, New York (2010); 30 Seconds off an Inch, The Studio Museum in Harlem, New York (2009); Thirty Americans, Rubell Family Collection, Miami (2008); Black Is, Black Ain’t, Renaissance Society at the University of Chicago (2008); 7e Biennale de l’Art Africaine Contemporaine, Dakar, Senegal (2006); Humor Me, H & R Block Artspace, Kansas City Art Institute, Kansas City, MO (2006); Relics and Remnants, Jamaica Center for Arts and Learning, Jamaica, NY (2006); Double Consciousness: Black Conceptual Art since 1970, Contemporary Arts Museum Houston (2005); The Interventionists: Art in the Social Sphere, Massachusetts Museum of Contemporary Art, North Adams (2004); Watch What We Say, Schroeder Romero, Brooklyn (2004); The Big Nothing, Institute of Contemporary Art, University of Pennsylvania, Philadelphia (2004); Only Skin Deep, International Center of Photography, New York (2004); and Out of Actions: Between Performance and the Object, 1949–1979, Museum of Contemporary Art, Los Angeles (1998).