Miller's first published work was in 1978 for Gold Key Comics on a comic based on the The Twilight Zone television series. He was soon working at DC and Marvel Comics, and in 1979 began illustrating Daredevil, where he would further develop his style and become one of the more notable comic creators of the 1980s. In the late 1980s he wrote and illustrated The Dark Knight Returns and wrote Batman: Year One for DC, stories which would help reshape the Batman character for years to come. In the early 1990s Miller began creating comics for Dark Horse Comics including a series of stories titled Sin City, a series that would eventually be made into a feature film.
Miller wrote the screenplay and co-directed the Sin City film, and has been involved in creating other films including writing the screenplays for RoboCop 2 and RoboCop 3 as well making cameo on-screen appearances in the films RoboCop 2, Daredevil, and Sin City.