Bob's first published comics were the self-published series MBLEH!, which ran to 3 issues and was the first Irish comic to be distributed by Diamond. He has also produced the majority of the content for The Shiznit, a free pocket-sized comic funded by adverts and released in various cities around Ireland. Other works include Robots Don't Cry (a children's illustrated book), a one-shot Freakshow special written by Rob Curley, and a series of silent strips in 2000AD under the banner "Bob Byrne's Twisted Tales". His most notable work to date is the original graphic novel Mr. Amperduke, a story told entirely in pictures without words, which Byrne published himself (trading as Clamnut Comix) in 2008. This character first appeared in a short story in MBLEH! in 2003, and was so well received that he followed the story with the graphic novel.
The first Mr. Amperduke story was reprinted in the small press of Judge Dredd Megazine #247 in 2006. This led to Byrne being commissioned to produce original stories for the Megazine's parent publication 2000 AD, using the same text-free storytelling technique.
Bob has stated on his blog that he will be contributing to an upcoming sketchbook collection under the title Eclectic Micks which will focus on several high-profile Irish artists. He plans to self-publish a collection of his two 24-Hour comics so far, and is also working on further children's books, although a release date has not yet been confirmed.