Andreyko co-wrote the limited series Torso with Brian Michael Bendis, for which he was nominated for the Angoulême International Comics Festival Prize Awarded by the Audience and the Prize for Scenario in 2003. He and Bendis are working with Paramount Pictures on a film adaptation of the work.

He co-created with P. Craig Russell, an Eisner- and Harvey-winning one-shot for Marvel Comics featuring Dr. Strange entitled What Is It That Disturbs You, Stephen?

In 1996, he directed a production of Joe Orton's Loot for the Weathervane Theater in Akron.

In 1997 he co-created (with Jay Geldhof and Galen Showman) The Lost, a Harvey-nominated comics mini-series which continued the story of Peter Pan in modern times, with the protagonist presented as an amoral vampiric boy prostitute.

He has written comics for other publishers, including Dark Horse Comics, IDW Publishing, and Todd McFarlane Productions/Image Comics.

In 2004 he began writing DC Comics' Manhunter series, relaunching it with a third volume, in which he introduced the character of Kate Spencer and her supporting cast. He co-created (with artist Jesus Saiz) Kate Spencer, the title character of the series, the first female character to carry the long-running legacy. He also created Spencer's civilian business partner Damon Matthews, who is in a romantic relationship with superhero Obsidian, one of the few gay-identified couples in mainstream superhero comics. Although #30 was listed as the final issue, the series resumed a year later with Michael Gaydos on art. However, the series was finally canceled with issue #38 in January 2009. Andreyko went to write the Manhunter back-up feature in DC Comics' Batman: Streets of Gotham monthly series that launched in June 2009.

Recent work includes The Ferryman for Wildstorm, created by Joel Silver, with artist Jonathon Wayshak.

Comics work includes:

• Torso (with Brian Michael Bendis, 5-issue limited series, Image Comics, 1998-199, tpb, 2001, ISBN 1582406979)
• Manhunter #1-38 (with Jesus Saiz/Jimmy Palmiotti and Michael Gaydos, DC Comics, 2004—2009) collected as:
• Street Justice (collects #1—5, December 2005, ISBN 1401207286)
• Trial By Fire (collects #6—14, January 2007, ISBN 1401211984)
• Origins (collects #15—23, August 2007, ISBN 1401213405)
• Unleashed (collects #24—30, January 2008, ISBN 1401216323)
• Forgotten (collects #31-38, May 2009)
• The Ferryman (with Jonathon Wayshak, 5-issue limited series, Wildstorm, 2008—2009)
• Batman: Streets of Gotham #1-13 (Manhunter Co-Feature only, DC Comics, 2009—2010)
• Michael Chiklis' Pantheon (5-issue limited series, IDW, 2010)