It was originally planned as a movie from New Line Cinema in 2007 with D. J. Caruso as the director David S. Goyer as a producer. Caruso and Carl Ellsworth wrote the script and Jeff Vintar did some rewrites. Shia LaBeouf wanted to star as Yorick Brown but turned it down saying that Yorick is far too similar to his Transformers character Sam Witwicky while Zachary Levi, who played the lead in the TV series Chuck, has expressed interest in playing Yorick as he is a fan of the comic book series, even going as far as having his character Chuck Bartowski read the Y: The Last Man graphic novel in the episode "Chuck Versus the Nacho Sampler" and Caruso wanted Alicia Keys for the part of Agent 355 and planning on using a real monkey and not a CGI construct, to play Ampersand. In 2012, Matthew Federman and Stephen Scaia entered final negotiations to write the film after Caruso left the film and J.C. Spink, Chris Bender and David Goyer were attached as producers while Mason Novick and Jake Weiner were picked as executive producers. Dan Trachtenberg was hired to direct the film in 2013 before the film got cancelled.

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