Busiek was born in Boston, Massachusetts. He grew up in various towns in the Boston area, including Lexington, where he befriended future comic book creator Scott McCloud. Busiek did not read comics as a youngster, as his parents disapproved of them. He began to read them regularly around the age of 14, when he picked up a copy of Daredevil #120. This was the first part of a continuity-heavy four-part story arc; Busiek was drawn to the copious history and cross-connections with other series. Throughout high school and college, he and McCloud practiced making comics.
During this time, Busiek also had many letters published in comic book letter columns, and originated the theory that the Phoenix was a separate being who had impersonated Jean Grey, and that therefore Grey had not died...a premise which made its way from freelancer to freelancer, and which was eventually used in the comics. Busiek explains, "A couple of years later, after I’d broken in, I attended my first convention as a pro, in Ithaca, New York, and I stayed at Roger Stern’s house. And we were talking about how much we liked the new X-Men, and he said, 'It’s just a pity there’s no way to bring Jean Grey back,' and I said, 'Sure there’s a way, there's always a way.'"
During the last semester of his senior year, Busiek submitted some sample scripts to editor Dick Giordano at DC Comics. None of them sold, but they did get him invitations to pitch other material to DC editors, which led to his first professional work, a back-up story in Green Lantern #162 (Mar. 1983).
Busiek has worked on a number of different titles in his career, including Arrowsmith, The Avengers, Icon, Iron Man, The Liberty Project, Ninjak, The Power Company, Red Tornado, Shockrockets, Secret Identity, Thunderbolts, Untold Tales of Spider-Man, JLA, and the award-winning Marvels and the Homage Comics title Kurt Busiek's Astro City.
In the 1990s, work on some of Busiek's more challenging, less mainstream projects, most notably Astro City, was repeatedly delayed by health problems brought about by mercury poisoning.
In 1997, Busiek began a stint as writer of Avengers alongside artist George Pérez. Pérez departed from the series in 2000, but Busiek continued as writer for two more years, collaborating with artists Alan Davis, Kieron Dwyer and others. Busiek's tenure culminated with the "Kang Dynasty" storyline. In 2003, Busiek re-teamed with Perez to create the JLA/Avengers limited series.
In 2003, Busiek began a new Conan series for Dark Horse Comics, which he wrote for four years.
In December 2005 Busiek signed a two-year exclusive contract with DC Comics. During DC's Infinite Crisis event, he teamed with Geoff Johns on a "One Year Later" eight-part story arc (called Up, Up and Away) that encompassed both Superman titles. In addition, he began writing the DC title Aquaman: Sword of Atlantis from issues 40-49. Busiek was the writer of Superman for two years, before followed by James Robinson starting from Superman #677. Busiek wrote a 52-issue weekly DC miniseries called Trinity, starring Batman, Superman and Wonder Woman. Each issue (except for issue #1) featured a 12-page main story by Busiek, with art by Mark Bagley, and a ten-page backup story co-written by Busiek and Fabian Nicieza, with art from various artists, including Tom Derenick, Mike Norton and Scott McDaniel.
Busiek will be teamed with Alex Ross on Dynamite Entertainment's Kirby: Genesis, an eight-issue miniseries set to debut in the first quarter of 2011. The series, which will be their first full collaboration since Marvels 17 years previous, will feature a large group of Jack Kirby's creator-owned characters, the rights to which were acquired by Dynamite, such as Silver Star, Captain Victory, Galaxy Green, Tiger 21 and the Ninth Men. Ross will co-plot the book, handle designs, and will oversee the book overall with Busiek, who will script the series.
Busiek's work has won him numerous awards in the comics industry, including the Harvey Award for Best Writer in 1998 and the Eisner Award for Best Writer in 1999. In 1994, with Marvels, he won Best Finite Series/Limited Series Eisner Award and the Best Continuing or Limited Series Harvey Award; as well as the Harvey Award for Best Single Issue or Story (for Marvels #4) in 1995. In 1996, with Astro City, Busiek won both the Eisner and Harvey awards for Best New Series. He won the Best Single Issue/Single Story Eisner three years in a row from 1996—1998, as well as in 2004. Busiek won the Best Continuing Series Eisner Award in 1997—1998, as well as the Best Serialized Story award in 1998. In addition, Astro City was awarded the 1996 Best Single Issue or Story Harvey Award, and the 1998 Harvey Award for Best Continuing or Limited Series.
Busiek was given the 1998 and 1999 Comics Buyer's Guide Awards for Favorite Writer, with additional nominations in 1997 and every year from 2000 to 2004. He has also received numerous Squiddy Awards, having been selected as favorite writer four years in a row from 1995 to 1998, and as a member of the favorite creative team for 1996, 1999, and 2003. In the Squiddy Awards, he was also named the favorite poster (among professional comics creators) to the rec.arts.comics.* newsgroups five years in a row from 2000 through 2004.