Quitely first worked upon the Scottish underground comics title Electric Soup in 1990. He wrote and drew The Greens, a parody of The Broons strip published by D.C Thompson.
Initially Electric Soup was only distributed locally in Glasgow, before being picked up by John Brown Publishing for widespread national UK distribution. This brought Quitely's work to the attention of Judge Dredd Megazine editor David Bishop. He was given work on Shimura and Missionary Man, quickly rising to prominence and being voted among the fans' favourite five artists in an end-of-year survey.
His big break into American comics was Flex Mentallo, a Doom Patrol spin-off written by fellow Glaswegian Grant Morrison for DC Comics' Vertigo imprint, in 1996. Quitely's work proved very popular, and this launched him onto more work for Vertigo. Initially he was put to work on strips for anthology titles such as Weird War Tales, and drew four issues of Jamie Delano's 2020 Visions, as well as various covers for DC. He later drew his first full length graphic novel, Batman: The Scottish Connection, with writer Alan Grant.
2000 saw Quitely and Morrison collaborate again, on JLA:Earth 2. Once again, the graphic novel was met with a hugely positive critical response, and later that year Quitely took over from Bryan Hitch as artist on The Authority, with Mark Millar as writer. Quitely left The Authority to draw New X-Men and also illustrate a Neil Gaiman-written story for the hardcover graphic novel, Sandman: Endless Nights.
Since leaving New X-Men, Quitely has drawn the mini series We3 in 2004, again in collaboration with Morrison. He shared the 2005 Best Penciller/Inker Eisner Award in a tie with artist John Cassaday for his work on the book. That same year, he and Morrison were also nominated for Best Limited Series for that book, and Quitely additionally was nominated for the Best Cover Artist Eisner for both We3 and Bite Club.
More recently, Quitely has illustrated All Star Superman. The twelve issue series, began publication in November 2005, and once again attracted near-unanimous praise. Quitely and Morrison's work on the series won them the Eisner Award for Best New Series in 2006, with Quitely collecting another nomination for Best Penciller/Inker. The series also won Best Continuing Series in 2007 and 2009.
Quitely is again working with Morrison on the new Batman and Robin title, which debuted in June 2009 after the "Battle for the Cowl" storyline.