In the UK, Milligan has contributed to numerous anthology titles including 2000 AD, Revolver, Eagle and A1, and helped launch the magazine Deadline.

In the US, he is best known for his frequent contributions to DC Comics' Vertigo imprint, which include the revamped DC properties Shade, the Changing Man and Human Target, a four-year run on the imprint's premier title Hellblazer, and original series Enigma, The Extremist, Egypt and Greek Street, as well as the Marvel series X-Statix, co-created by Milligan and artist Mike Allred.

Concurrently, Milligan, Ewins and Brendan McCarthy had been working on the anthology title, Strange Days for Eclipse Comics.

Milligan, McCarthy and Ewins produced three issues of this psychedelic comic, it was not a great seller but it picked up a small, loyal readership.

[3] Skreemer was a six-issue mini-series (May 1989 – October 1989) drawn by Brett Ewins that was somewhat lost in the midst of the so-called "British Invasion" of American comics of the time.

[3] Milligan succeeded Grant Morrison on Animal Man for a six-issue run in 1990–1991,[6] and became the regular writer of Batman in Detective Comics in the same year.

[7] Skin (art by Brendan McCarthy) was the story of a young thalidomide skinhead in 1970s London, and his attempts to deal with his disability and the world in general.

[2] The strip was due to feature in Crisis in 1990 but the publishers Fleetway were worried by the controversial subject matter, plus they were concerned with the use of explicit language in the story.

[14] Milligan spent the remainder of the decade writing one-off specials such as Face and The Eaters, or miniseries like Egypt and Tank Girl The Odyssey (with its co-creator Jamie Hewlett providing art), as well as acting as advisory editor to Paul Honeyford's Fighting Figurines.

Milligan and Brendan McCarthy's psychedelic comic Rogan Gosh was reprinted in a collected edition by Vertigo in 1996,[3] after being first serialised six years earlier in Revolver.

[15] In 2006, he wrote the X-Statix Presents: Dead Girl five-issue miniseries for Marvel collaborating with artist Nick Dragotta and co-creator Mike Allred.

The following year he wrote an Infinity, Inc. limited series for DC[20] and The Programme for Wildstorm, starring a Soviet Cold War superhero.

[26] In 2010, Milligan was announced as the writer for Batman #703, a prelude to the "Bruce Wayne: The Road Home" crossover storyline,[27] although he later clarified that he was not involved in the production of the issue.