Fowler is the author of the Bryant and May mysteries, in which the two detectives, Arthur Bryant and John May, are members of the fictional Peculiar Crimes Unit, based on a unit his father worked in during World War II. The series comprises: Full Dark House, The Water Room, Seventy-Seven Clocks, Ten Second Staircase, White Corridor, The Victoria Vanishes, Bryant & May On the Loose, Bryant & May Off the Rails, Bryant & May and the Memory of Blood, Bryant & May and the Invisible Code, Bryant & May and the Bleeding Heart, Bryant & May and the Burning Man, Bryant & May: London's Glory, Bryant and May: Strange Tide and Bryant and May: Wild Chamber, with further volumes to follow. The series is also available in audiobook format, narrated by Tim Goodman. Bryant and May, as well as other characters from this series, also appear in Fowler's Rune, Darkest Day, and Soho Black, although these books are not considered part of the series.
The Bryant and May series is set primarily in London, with stories taking place in various years between World War II and the present. While there is a progressive narrative, each of the cases stand alone as separate stories. The exceptions are: Full Dark House, an origin story which focuses on John May's reminiscence of the team's first case together during the Blitz, Seventy Seven Clocks, framed as Arthur Bryant's retelling of a case from 1973, and On The Loose and Off The Rails, which continue characters and events across two books.
Fowler weaves many factual layers of London's history and society throughout the series. Most of the locations are recognisable London landmarks such as St Paul's Cathedral, the Tate Gallery and various theatres. A major feature of The Water Room is the networks of tunnels and underground rivers underneath the city. London can be considered a separate character in the novels
There are many references to other literary works throughout the series. Seventy-Seven Clocks contains references to Gilbert and Sullivan throughout the narrative, while The Victoria Vanishes has similarities with The Moving Toyshop by Edmund Crispin. Other puzzles, paradoxes and jokes are tucked into the narratives, rewarding regular readers.
His book Rune is an update to a modern setting of the M. R. James story Casting the Runes. It also features Bryant, May, and several characters from that series.
His story "The Master Builder" was filmed as Through the Eyes of a Killer, starring Richard Dean Anderson, Marg Helgenberger and Tippi Hedren. His tenth short story collection, Old Devil Moon, won the Edge Hill Audience Prize 2008. His short story 'Left Hand Drive' was made into a film that won Best British Short. His stories 'On Edge' and 'The Most Boring Woman In The World' were both filmed. His novella Breathe won the British Fantasy Society Award for best novella in 2005.
Put into different temporal settings, some elements of his original 2008 story “Arkangel” from Exotic Gothic 2 reappear in his 2012 frame-novel Hell Train (a book called “must read now!” by SciFiNow), including the Polish town of Chelmsk, and the physical descriptions of its white gold-rivetted damnation train Arkangel, and the town’s yokels.
His memoir of a lonely 1960s childhood, Paperboy, won the inaugural Green Carnation prize, which celebrates fiction and memoirs written by gay men. A sequel, 'Film Freak', charted his travels through the British film industry. His collection ‘Red Gloves’ consisted of 25 new stories marking a quarter-century in print, two graphic novels and a Hammer horror radio play. He also wrote a Sherlock Holmes audio drama for BBC 7 entitled The Lady Downstairs and the War Of The Worlds videogame with Sir Patrick Stewart, for Paramount.
Fowler wrote a periodic column for The Independent titled "Invisible Ink". In this series, he looked at a wide range of writers whose works, once popular, have now fallen out of the public eye. His book version, The Book of Forgotten Authors, is published by Quercus.