The Detroit native died Monday, a day after his birthday, DC Comics said. His cause and place of death weren't immediately known.
McDuffie wrote comics for the New York-based DC and Marvel, including runs on Batman: Legends of the Dark Knight, the Fantastic Four and the Justice League of America. He also penned several animated television shows and features, including the just-released "All-Star Superman" as well as "Justice League: Crisis on Two Earths" and the animated TV series "Static Shock" and "Ben 10: Alien Force."
News of McDuffie's death was first reported Tuesday by the website Comic Book Resources. As recently as last week, McDuffie attended the premieres of the new "All-Star Superman" film in Los Angeles and New York, and was scheduled to appear at an event Wednesday at Golden Apple Comics in Los Angeles.
Instead, there would be a remembrance at the launch party that McDuffie was supposed to attend, said film director Reginald Hudlin, a friend of about 15 years who was debuting a new project.
McDuffie's work for Marvel included "Damage Control," which took a serious but fictional look at a company whose job it was to clean up the damage - both physical and legal - resulting from battles between superheroes and supervillains. In 1992, however, he helped form the comic book company Milestone Media Inc., which gave him the freedom and leeway to create his own characters, many of whom were of differing ethnic backgrounds.
Milestone Media focused on creator-owned multicultural superheroes including "Hardware," "Icon," "Blood Syndicate," "Xombi" and "Static," which was turned into the popular children's cartoon "Static Shock," on which he served as a story editor.
McDuffie also wrote for other titles and characters, too, including Black Panther and Deathlok.
His work at Milestone set a new tone for the use of multicultural characters in the pantheon of heroes, something that lent itself to his television work, too, where characters of color became part of interlocking teams.
Besides comics, McDuffie was a producer and story editor on Cartoon Network's "Justice League Unlimited," and wrote and produced episodes of other cartoons, including "What's New, Scooby Doo?," "Ben 10: Ultimate Alien" and "Teen Titans."
Christopher Chambers, a journalism professor at Georgetown University and author of the graphic novel "The Darker Mask," told The Associated Press that McDuffie's influence resonated in animation and comic books.
"For minorities in this mode of entertainment ... he was a hero, he was a pioneer," Chambers said Tuesday. "Not just for we who are fans but also for content creators. He spilled over into other media."
Bruce Timm, executive producer of the DC Universe animated original movie series, heaped praise on McDuffie's talents and character.
"As a writer he was simply brilliant - adventurous, effortlessly funny, ferociously smart. As a person, he was all that and much, much more - more, in fact, than my puny words can even hope to express," Timm said.
McDuffie was nominated for two Emmy Awards for "Static Shock," a Writers Guild award for "Justice League" and three Eisner awards for his work in comic books, his website said.
Organizers of Seattle's annual Emerald City Comicon said they planned to hold a memorial panel remembering McDuffie at the three-day event on March 5.
Dan DiDio, co-publisher of DC Entertainment, said McDuffie "left a lasting legacy on the world of comics that many writers can only aspire to. He will not only be remembered as an extremely gifted writer whose scripts have been realized as comics books, in television shows and on the silver screen, but as the creator or co-create of so many of the much-loved Milestone characters, including Static Shock."
Tom Brevoort, Marvel's senior vice president for publishing, said McDuffie was a force behind bringing more diversity into comics.
"He was very interested in creating a wider range of multiculturalism in comics, having been profoundly affected by the example of the Black Panther when he was growing up, and wanting to give that same opportunity to others of all races, creeds and religions, which is one of the reasons he left Marvel and co-founded Milestone," Brevoort told the AP. "And he eventually came back to write both Beyond! and Fantastic Four for me."
McDuffie is survived by his wife, Charlotte, and his mother, Edna McDuffie-Gardner.
Associated Press writers Sonya Ross and Jesse Holland in Washington contributed to this report.