Ennis began his comic writing career in the late 1980s with the series Troubled Souls. Appearing in the short lived but critically acclaimed British anthology Crisis, it told the story of a young, apolitical protestant man caught up by fate in the violence of the Irish 'Troubles'. Ennis shortly after began to write for Crisis' parent publication, 2000 A.D. He quickly graduated on to the title's flagship character, Judge Dredd, whose strip he scripted on and off for a number of years. He was poached by American publishers DC Comics in the mid 1990s, for whom he has written a number of titles.
Ennis' landmark work to date is the sixty six-issue epic Preacher, which he co-created with artist Steve Dillon. The highly original tale of a dissillussioned preacher with supernatural powers (literally) searching for a God who has abandoned His creation, it drew plaudits for Ennis from all sections of the media; the Guardian newspaper voted one of the Preacher collections its book of the week, and film director Kevin Smith described it as "Better than a night at the movies." Other titles Ennis has scripted include Hellblazer, Hitman, and, for Marvel Comics, The Punisher.