Mignola was born in Berkeley, California. He began his career in 1980 by illustrating spots in The Comic Reader. His first published piece was in The Comic Reader #183, a spot illustration of Red Sonja (pg. 9). His first published front cover was The Comic Reader #196 in November 1981. In 1982 he graduated from the California College of the Arts with a BFA in Illustration.
In 1983 he worked as an inker at Marvel Comics on Daredevil and Power Man and Iron Fist and later on titles such as The Incredible Hulk, Alpha Flight, and the Rocket Raccoon limited series.
In 1987, he began working for DC Comics as well. He drew the Phantom Stranger and World of Krypton limited series. With writer Jim Starlin, Mignola produced the Cosmic Odyssey miniseries in 1988. Mignola drew covers for several Batman stories, including "Batman: A Death in the Family" and "Dark Knight, Dark City". Writer Brian Augustyn and Mignola crafted the Gotham by Gaslight one-shot in 1989. Through the early 1990s Mignola worked on covers and backup features for various DC and Marvel Comics. He collaborated twice with writer Howard Chaykin. In 1990-1991, they produced the Fafhrd and the Gray Mouser limited series for Epic Comics, with inker Al Williamson. This was followed with the Ironwolf: Fires of the Revolution graphic novel in 1992.
Prior to 1994 Mignola had done work-for-hire illustration. That year, Dark Horse Comics released Hellboy: Seed of Destruction, Mignola's creator-owned project. Though he wrote the story himself, it was scripted by John Byrne. The next Hellboy story, The Wolves of Saint August, was completely written and drawn by Mike Mignola. Since then all Hellboy stories have been written solely by Mike Mignola with the exception of They That Go Down to the Sea in Ships which was co-written by Joshua Dysart.
Makoma (2006) was the first Hellboy story not drawn by Mignola, featuring the art of Richard Corben. Corben would return to draw many flashback stories for the series. Other artists have also had a hand in drawing flashback stories including Jason Shawn Alexander, Kevin Nowlan and Scott Hampton. In 2007, following after 2005's The Island, British artist Duncan Fegredo took over art duties on the ongoing story arc of Hellboy from Darkness Calls onwards.
Mike Mignola returned as the full-time artist for Hellboy in 2012 for the ongoing series, Hellboy in Hell. The series is currently published sporadically, but multiple-issue stories are monthly.
In 1998 the first Hellboy spin-off, Abe Sapien, was launched. It was not written by Mike Mignola, but it did feature his Hellboy short story "Heads" as a back-up. Abe Sapien did not take off properly until a decade later in 2008's The Drowning. Since then it has had several short stories and beginning in 2013 it became an ongoing series with Scott Allie as the lead writer with Mignola.
Lobster Johnson was the next spin-off, debuting as a back-up feature in 1999's Box Full of Evil. The series got its own title later in 2007's Lobster Johnson: The Iron Prometheus. It returned again with the miniseries The Burning Hand in 2012, followed by various short stories.
B.P.R.D. was the third spin-off, but it was the first one which was conceived to be more than just a one-off side story, but rather a series of stories. It began with 2002's Hollow Earth, which continued on from Hellboy: Conqueror Worm. Beyond that followed as series of short stories designed to explore what the B.P.R.D. series could be. 2004's Plague of Frogs was the story that solidified what the series was, and would set the direction for future books to come, so much so that the first major story cycle is collected in omnibus editions titled B.P.R.D.: Plague of Frogs. A vast majority of the stories in this era were co-written with John Arcudi and drawn by Guy Davis.
B.P.R.D. Hell on Earth is the main series continuing after the catastrophic events at the conclusion of the Plague of Frogs cycle. Guy Davis left the series in 2011 with the conclusion of Hell on Earth: Gods. Tyler Crook became the new ongoing artist beginning with Hell on Earth: Monsters, but he is joined by several regular artists, most notably James Harren.
Sir Edward Grey, Witchfinder (more commonly known simply as "Witchfinder") began with a teaser story in 2008's MySpace Dark Horse Presents #16, followed by a full miniseries in 2009. It follows the stories of the occult investigator, Sir Edward, agent of Queen Victoria.
Sledgehammer 44 is the most recent addition to the Hellboy Universe. It is about a Vril Energy Suit, like the one first introduced in Lobster Johnson: The Iron Prometheus, in World War II.
Baltimore is a series begun with a 2007 illustrated novel, and continued as a comic book series. It was created by Mike Mignola and Christopher Golden.
Alan Moore has described Mignola's style as "German expressionism meets Jack Kirby". His style has also been likened to an amalgamation of Jack Kirby and Alex Toth.
Mignola worked as an illustrator for Francis Ford Coppola's 1992 movie Bram Stoker's Dracula. He was also the production designer for the Disney feature film, Atlantis: The Lost Empire in 2001, and was a concept artist for 2002's Blade II, also directed by del Toro, and a concept artist for Pixar's Brave.
Mignola was hired by Bruce Timm to provide character designs for Batman: The Animated Series in 1991. His redesign of Mr. Freeze was used for the series.
Mignola's design of the 1880s Batman costume from the comic Batman: Gotham by Gaslight appeared in Batman: The Brave and the Bold.
Hellboy was made into a feature film in 2004 by director Guillermo del Toro. Mignola was closely involved with the movie's production, and a sequel was released in 2008. Recently, Hellboy has been made into two direct-to-video animated films, Sword of Storms in 2006 and Blood and Iron in 2007.
Mignola's The Amazing Screw-On Head debuted in 2006 on the Sci-Fi Channel, starring the voices of Paul Giamatti and David Hyde Pierce.
In May 2017 it was announced that Mignola will co-write the script for Hellboy: Rise of the Blood Queen, an R rated reboot film that will be directed by Neil Marshall and star David Harbour as Hellboy.1995:
Won "Best Writer/Artist" Eisner Award, for Hellboy: Seed of Destruction
Won "Best Graphic Album: Reprint" Eisner Award, for Hellboy: Seed of Destruction
Won "Best Artist" Harvey Awards
Won "Best Achievement by an Inker" Don Thompson Award
Won "Best Artist" Harvey Awards
Won "Best Graphic Album of Previously Released Material" Harvey Awards, for Hellboy: The Wolves of Saint August
Won "Best Writer/Artist" Eisner Award, for Hellboy: Wake the Devil
Won "Best Writer/Artist" Eisner Award, for Hellboy: Almost Colossus, Hellboy Christmas Special and Hellboy Jr. Halloween Special
Won "Best Artist" Harvey Award, for Hellboy: Box Full of Evil
Won "Best Finite Series/Limited Series" Eisner Award, for Hellboy: Conqueror Worm
Won "Best Humor Publication" Eisner Award, for The Amazing Screw-On Head
Won "Best Short Story" Eisner Award, for "The Magician and the Snake"
Won "Favourite Comics Writer/Artist" Eagle Award
Won "Best Comics-Related Book" Eisner Award, for The Art of Hellboy
Received "Inkpot Award"
Won "Favourite Comics Writer/Artist" Eagle Award
Won "Roll of Honour" Eagle Award
Won "Favourite Colour Comicbook – American" Eagle Award, for Hellboy: Darkness Calls
Won "Best Cover Artist" Harvey Awards
Won "Award for Favourite Colour Comicbook – American" Eagle Award
Won "Roll of Honor" Eagle Awards
Won "Best Horror Comic Book" Rondo Hatton Classic Horror Awards, for Hellboy: In the Chapel of Moloch
Won "Best Finite Series/Limited Series" Eisner Award, for Hellboy: The Crooked Man
Won "Best Graphic Album: Reprint" Eisner Award, for Hellboy Library Edition, vols. 1 and 2
Won "Best Publication Design" Eisner Award, for Hellboy Library Edition, vols. 1 and 2
Won "All-in-One Award" Inkwell Awards
Won "Best Cover Artist" Harvey Awards, for Hellboy: Bride of Hell
Won "Favorite Writer/Artist" Eagle Award
Won "Favorite Artist:Inks" Eagle Award
Won "Best Single Issue (or One-Shot)" Eisner Award, for Hellboy: Double Feature of Evil