Rennie is most well known in the comics field for his work on British perennial comics powerhouse anthology series 2000 AD, where he eventually ascended to the unofficial rank of "number two" Judge Dredd writer for the series over time. In addition to his comic strips for 2000 AD, Rennie created White Trash: Moronic Inferno, and novels for Warhammer Fantasy.
Rennie's first work was published in Blast! magazine in 1991; a metafictional Sherlock Holmes story called "Sherlock Holmes in the Curious Case of the Vanishing Villain", painted by Woodrow Phoenix. It also featured appearances by characters from other Victorian fiction including Dr Jekyll and Mr Hyde and characters from stories by Edgar Allan Poe.
He then showed his surprising range with the completely different White Trash in the same issue - a satirical journey through the USA, drawn by the New Zealand artist Martin Emond. Both these stories were later collected into one-shot graphic novels and published by Tundra Publishing. Two further planned collaborations with Phoenix, a one-shot graphic novel called "Orson Welles: Special Agent!" and Necronauts, later completed with Frazer Irving,were halted when Tundra Press ceased publishing in 1993.
Rennie's first major series for the 2000 AD family was Missionary Man, which began in Judge Dredd Megazine vol.2 #29 (5/93) and ran between "the Meg" and 2000 AD for 74 episodes before finishing in 2002. Other original series have included Witch World (1997) and Rain Dogs (2000). He also took over the exploits of the perennial Judge Dredd villain Mean Machine (2000–01), as well as the return of the original Rogue Trooper (2002–04).
Among his most celebrated work for 2000 AD is the miniseries Necronauts (2000–01), in which Harry Houdini, Arthur Conan Doyle, Charles Fort, and (inevitably) H. P. Lovecraft team up to defeat an incomprehensibly alien menace that seeks to destroy the human race. This was quickly followed up by the ongoing series Caballistics, Inc. (41 episodes as of August 2005), a story about a recently privatized team of occult researchers, which pleased fans with its combination of pop-cultural references and labyrinthine conspiracies.
By 2004, Rennie had become the "number two" writer on the Judge Dredd strip, following up a number of subplots initiated by its principal author—and fellow A/P/AVP contributor—John Wagner, as well as developing his own situations and guest characters, some of whom have spun off into popular stories of their own. While the lengthier, "epic" Judge Dredd adventures are typically scripted by Wagner, Rennie was awarded one in 2005. This story, "Blood Trails," ran for ten episodes beginning in 2000 AD prog 1440 (5/25/05).
His novels for Warhammer, both Fantasy and 40k, include Zavant, Ulli and Marquand, the Kal Jerico stories, Bloodquest, and Execution Hour and Shadow Point for Battlefleet Gothic.
Rennie has done a lot of work on computer games and was nominated for the 2006 BAFTA for his script on the Rogue Trooper game. He is moving away from comics and into more video game work, in May 2008 he was quoted as saying "I got fed up with comics and quit last month to concentrate on games." Although he later said he was misquoted, and that he hasn't completely given up comics, as he will still be writing an ongoing series for 2000 AD. He has a number in the works, as well as planning a novel on the Romans in Scotland.
He is known for maintaining close links with the fan community, for example by contributing to small press comics such as Solar Wind, despite a public persona he describes as "a grumpy Scottish git".
In May 2008 he announced he was quitting comics to concentrate full-time on videogames which "are more fun, pay better and have a brighter future."