Enrique Breccia, the son of one of the greatest Latino-American artists of all time, Alberto Breccia, drew his first work in 1968, when together with his father he illustrated La Vida del Che, a biography of the famous revolutionary Che Guevara written by Héctor Germán Oesterheld. In 1972 he started his collaboration with the British publishing house Fleetway, drawing the comic book Spy 13 under a pseudonym, and later a series of war stories for the Italian magazine Linus.

His collaboration with writer Carlos Trillo began in 1976 with the comic El Buen Dios, immediately followed by Alvar Mayor, his most famous character with whom he entered the world comic book scene. He had several other successful collaborations with Trillo, the mini series El peregrino de la Estrellas, the surreal series Los Viajes del Marco Mono and the painted El Reino del Azul. In 1983 he drew Ibáñez from the script of Robin Wood, and the next year the highly successful El Sueñero and El Cazador del Tiempo from his own scripts. He also drew several comic book adaptions of famous novels such as Till Eulenspiegel, Treasure Island and Moby Dick. In 1987 he published the graphic novel Lope de Aguirre and in 1995 De Mar a Mar.

In 2000 he began his collaboration with American comic book publishers, working on an issue of X-Force for Marvel , and Legion Worlds and Batman: Gotham Knights for DC Comics. In 2002 he drew the graphic novel Lovecraft, about the life of writer H.P. Lovecraft written by Hans Rodionoff, for DC comics' Vertigo imprint. In 2005 he became the head artist for the Vertigo series Swamp Thing, drawing 22 issues till 2007.

He currently lives in New York, and is working on the second volume of the comic book saga Sentinelles for the French market, written by Xavier Dorison.