Reeve studied illustration, first at Cambridgeshire College of Arts and Technology (CCAT - now Anglia Ruskin University), where he contributed a comic strip to the Student Union magazine, and later at Brighton Polytechnic (now the University of Brighton). Before becoming a professional illustrator he worked at a bookshop in Brighton for several years. During his student years and for a few years afterwards he wrote for and performed in comedy sketch shows with a variety of collaborators under various group names, among them The Charles Atlas Sisters.

He provided cartoons for many books including those in the Horrible Histories and the Murderous Maths series and wrote the Buster Bayliss series series of books for young readers, which currently includes Night of the Living Veg, The Big Freeze, Day of the Hamster, and Custardfinger. He is also the author and illustrator of a Dead Famous book, Horatio Nelson and His Victory.

His first book for older readers was Mortal Engines which won the Nestlé Smarties Book Prize Gold Award and was shortlisted for the Whitbread Book Award. Mortal Engines is the first book in the Mortal Engines Quartet series, which also includes Reeve's Predator's Gold, Infernal Devices and A Darkling Plain. The books are about the lives of two young adventurers, Tom Natsworthy and Hester Shaw, who live in a lawless post-apocalyptic world inhabited by moving cities.

Mortal Engines took Reeve over a decade to write. He started coming up with ideas for the book between 1989 and 1990, and it was first published in 2001. This was because he was working at it part time, between illustration jobs. After it was published, however, he cut down on his illustration work and devoted his more of his time to writing, as he now knew he could fully complete a project.

His 2007 novel, Here Lies Arthur, an alternative version of the Arthurian legend, was awarded the Carnegie Medal. The first novel of his steampunk series set in outer space, Larklight, was under development as a film directed by Indian director Shekhar Kapur, but the director is no longer attached. Reeve himself professes that, when planning out stories for his novels, "I see it as a film that I run in my head, and I just keep running alternative versions of it until I come up with a cut I like." The future of the film is in the new hands of Swedish director Tomas Alfredson.

Reeve claims not to be a methodical writer. He does not plan anything at all, usually starting with an opening image, a closing image, and a few vague notions for the things that happen in between. This leads to thousands of words of rough draft material being abandoned - even entire novels, such as with Fever Crumb and Mortal Engines. He does, however take ideas from these abandoned drafts to build the final version. It usually takes him a year to get a novel from first idea to publication, six months of which are spent actively writing it. The rest of the time is spent on editing and thinking.

Buster Bayliss series

• Night of the Living Veg (2002)
• The Big Freeze (2002)
• Day of the Hamster (2002)
• Custardfinger! (2003)

Mortal Engines Quartet

(Marketed as "The Hungry City Chronicles" in the U.S.)

• Mortal Engines (2001)
• Predator's Gold (2003)
• Infernal Devices (2005)
• A Darkling Plain (2006)

• Fever Crumb (2009) A prequel set generations before the Mortal Engines quartet and dealing with the events that occurred shortly before London became the first Traction City and the development of the technology used to create it.
• A Web of Air (2010) The sequel to the prequel Fever Crumb.
• Scrivener's Moon (2011) release date TBC.

• Untitled short story covering Anna Fang's past, written for World Book Day 2011.

Larklight trilogy

• Larklight (2006)
• Starcross (2007)
• Mothstorm (2008)

Other novels

• Horatio Nelson and His Victory (2003)
• Here Lies Arthur (2007)
• No Such Thing As Dragons (2009)

Books as illustrator

• Pantsacadabra! (2006) (with Kjartan Poskitt)
• Urgum the Axeman (2006) (with Kjartan Poskitt)
• Murderous Maths (series) (with Kjartan Poskitt)
• Awful Art (1997) (with Michael Cox)
• No Such Thing As Dragons (2009) (own book)