While in college, Spencer wrote three pitches to Marvel Comics soon after the Marvel Knights imprint launched in 1998.According to Spencer, "Joe [Quesada] didn’t like the first two but the third one was a Black Cat pitch that was a Jackie Brown kind of Tarantino-esque thing. He said he liked that one but they weren’t going to do anything with anybody new at the time." After another pitch was rejected, this time by Oni Press, Spencer went on to work in other fields, including politics and music, before he successfully pitched Existence 2.0 to Jim Valentino of Image Comics. The first issue was released in July 2009. A second miniseries, Existence 3.0, followed in November.In 2010, Paramount Pictures acquired the rights to Existence 2.0, and a film is in development through Platinum Dunes with Miles Millar and Alfred Gough to adapt and executive produce.

Spencer also wrote Forgetless and Shuddertown at Image. An A.V. Club review of Shuddertown stated that Spencer "has become one of the finest practitioners" of crime noir in comics.Spencer's first ongoing series, Morning Glories, was released in August 2010. He is also scheduled to write a pair of series at DC Comics: a Jimmy Olsen co-feature beginning in September's Action Comics #893, and a T.H.U.N.D.E.R. Agents monthly debuting in November.

DC Comics

• Action Comics #893-up - "Jimmy Olsen" co-feature (begins September 2010)
• T.H.U.N.D.E.R. Agents #1-up (begins November 2010)

Image Comics

• Existence 2.0 #1-3 (2009)
• Existence 3.0 #1-4 (2009—2010)
• Forgetless #1-5 (2009—2010)
• Fractured Fables (OGN) - "Cinderella" (2010)
• Morning Glories #1-up (2010—present)
• Shuddertown #1-4 (2010)