His family attorney confirmed the passing of the Marvel legend at Cedars-Sinai Medical Center in Los Angeles on Monday.
Lee revolutionized the comics by introducing human frailties in superheroes such as Spider-Man, The Fantastic Four and The Incredible Hulk as the top writer at Marvel Comics and later as its publisher.
He revived the industry in the 1960s by offering the costumes and action craved by younger readers while insisting on sophisticated plots, college-level dialogue, satire, science fiction, even philosophy. In later years, Spider-Man, the Hulk, X-Men and other Lee creations found new life as stars of blockbuster films.
Many of Lee's characters had roots in New York City, where he was born in Manhattan in 1922. His parents were Romanian-born immigrants and he grew up living in various apartments on the Upper West Side, Washington Heights and in the Bronx. He attended DeWitt Clinton High School in the Bronx.
Stan Lee created some of the most incredible and enduring characters of our time, and he chose New York City as the place to tell their stories. On behalf of his hometown, I want to express our deepest condolences to his family and loved ones.— Mayor Bill de Blasio (@NYCMayor) November 12, 2018
"I think everybody loves things that are bigger than life. ... I think of them as fairy tales for grown-ups," he told The Associated Press in a 2006 interview. "We all grew up with giants and ogres and witches. Well, you get a little bit older and you're too old to read fairy tales. But I don't think you ever outgrow your love for those kind of things, things that are bigger than life and magical and very imaginative."
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Fresh out of high school at age 16 in the late 1930s, Lee got a job as an assistant at Timely Comics, which would eventually become Marvel Comics.
In 1941, he made his comic debut writing a Captain America book, and used the pseudonym "Stan Lee" for the first time. His real name was Stanley Martin Lieber.
Lee considered the comic-book medium an art form and he was prolific: By some accounts, he came up with a new comic book every day for 10 years.
"I wrote so many I don't even know. I wrote either hundreds or thousands of them," he told the AP in 2006.
Timely Comics became Marvel in the 1960s, when Lee hit his stride bringing the Fantastic Four, the Hulk, Spider-Man, Iron Man and numerous others to life.
"It was like there was something in the air. I couldn't do anything wrong," he recalled.
Lee scripted most of Marvel's superhero comics himself during the '60s, including the Avengers and the X-Men, two of the most enduring. In 1972, he became Marvel's publisher and editorial director; four years later, 72 million copies of Spider-Man were sold.
"He's become our Mickey Mouse," he once said of the masked, web-crawling crusader.
Unlike competitor DC Comics, Lee's heroes were a far cry from virtuous do-gooders such as Superman. The Fantastic Four fought with each other. Spider-Man was goaded into superhero work by his alter ego, Peter Parker, who suffered from unrequited crushes, money problems and dandruff. The Silver Surfer, an alien doomed to wander Earth's atmosphere, waxed about the woeful nature of man. The Hulk was marked by self-loathing. Daredevil was blind and Iron Man had a weak heart.
Lee's direct influence faded in the 1970s as he gave up some of his editorial duties at Marvel. But with his trademark white mustache and tinted sunglasses, he was the industry's most recognizable figure. He lectured widely on popular culture.
Lee moved from his homes in Manhattan and on Long Island to Los Angeles in 1981 to head Marvel Productions, an animation studio that was later purchased, along with Marvel Comics, for $50 million by New World Entertainment.
As sales of comics declined, Marvel was forced into bankruptcy proceedings that meant it had to void a lifetime contract prohibiting Lee from working for anyone else. Lee later sued Marvel for $10 million, saying the company cheated him out of millions in profits from movies based on his characters.
In 2000, Lee agreed to write stories for DC Comics, reinventing Superman, Batman, Wonder Woman and other signature characters for Marvel's one-time rival.
The Walt Disney Company acquired Marvel Entertainment for US$4 billion in 2009 and his characters found new life in a series of blockbuster movies, making 20 since the purchase and more on the way.
Walt Disney Company Chairman and CEO Bob Iger released a statement: "Stan Lee was as extraordinary as the characters he created. A super hero in his own right to Marvel fans around the world, Stan had the power to inspire, to entertain, and to connect. The scale of his imagination was only exceeded by the size of his heart."
Lee became more of a figurehead in later years, but also something of a cult icon. Starting in 1989, he made one of his first cameos in "The Trial of the Incredible Hulk," and he went on to be featured in every Marvel movie following 2000s "X-Men" often delivering his trademark motto, "Excelsior!" (The name of his autobiography and the official motto of the state of New York.)
Recent projects Lee helped make possible range from the Disney Marvel films "Avengers: Infinity War," ''Black Panther" and "Guardians of the Galaxy" to such TV series as ABC's "Agents of S.H.I.E.L.D" and "Daredevil."
“Stan Lee was as extraordinary as the characters he created. A super hero in his own right to Marvel fans around the world, Stan had the power to inspire, to entertain, and to connect." –Bob Igerhttps://t.co/pLTKx1R0dF pic.twitter.com/Uj9fqHpZXg— Disney (@Disney) November 12, 2018
Joan Clayton Boocock Lee, to whom he was married for more than 60 years, died last year.
He is survived by his daughter, J.C.
Celebrities and notable figures who have recently passed away
Information from ABC News and The Associated Press
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