Stanley Martin Lieber was born on December 28, 1922, in Manhattan, New York City, in the apartment of his Romanian-born Jewish immigrant parents, Celia (née Solomon) and Jack Lieber, at the corner of West 98th Street and West End Avenue in Manhattan.

By the time Lee was in his teens, the family was living in an apartment at 1720 University Avenue in The Bronx. Lee described it as "a third-floor apartment facing out back". Lee and his brother shared the bedroom, while their parents slept on a foldout couch.

Stan said that in his youth he worked such part-time jobs as writing obituaries for a news service and press releases for the National Tuberculosis Center; delivering sandwiches for the Jack May pharmacy to offices in Rockefeller Center; working as an office boy for a trouser manufacturer; ushering at the Rivoli Theater on Broadway, and selling subscriptions to the New York Herald Tribune newspaper.

At fifteen, Lee entered a high school essay competition sponsored by the New York Herald Tribune, called "The Biggest News of the Week Contest." Lee claimed to have won the prize for three straight weeks, goading the newspaper to write him and ask him to let someone else win. The paper suggested he look into writing professionally, which Lee claimed "probably changed my life."

Stan graduated from high school early, aged sixteen and a half, in 1939 and joined the WPA Federal Theatre Project.

With the help of his uncle Robbie Solomon, Lee became an assistant in 1939 at the new Timely Comics division of pulp magazine and comic-book publisher Martin Goodman's company. Timely, by the 1960s, would evolve into Marvel Comics.

Marshaling his childhood ambition to be a writer, young Stanley Lieber made his comic-book debut with the text filler "Captain America Foils the Traitor's Revenge" in Captain America Comics #3 (cover-dated May 1941), using the pseudonym Stan Lee which years later he would adopt as his legal name.

Stan graduated from writing filler to actual comics with a backup feature, "'Headline' Hunter, Foreign Correspondent", two issues later. Lee's first superhero co-creation was the Destroyer, in Mystic Comics #6 (August 1941). Other characters he co-created during this period fans and historians call the Golden Age of Comic Books to include Jack Frost, debuting in the U.S.A. Comics #1 (August 1941), and Father Time, debuting in Captain America Comics #6 (August 1941).

When Simon and his creative partner Jack Kirby left late in 1941, following a dispute with Goodman, the 30-year-old publisher installed Lee, just under 19 years old, as interim editor. The youngster showed a knack for the business that led him to remain as the comic-book division's editor-in-chief, as well as art director for much of that time, until 1972, when he would succeed Goodman as publisher.

Lee entered the United States Army in early 1942 and served within the US as a member of the Signal Corps, repairing telegraph poles and other communications equipment. He was later transferred to the Training Film Division, where he worked writing manuals, training films, slogans, and occasionally cartooning.

From 1945 to 1947, Lee lived in the rented top floor of a brownstone in the East 90s in Manhattan.

Stan married Joan Clayton Boocock, originally from Newcastle, England, on December 5, 1947.

In 1949, the couple bought a house in Woodmere, New York, on Long Island, living there through 1952. Their daughter Joan Celia "J. C." Lee was born in 1950. Another daughter, Jan Lee, died a few days after her birth in 1953.

In the mid-1950s, by which time the company was now generally known as Atlas Comics, Lee wrote stories in a variety of genres including romance, Westerns, humor, science fiction, medieval adventure, horror and suspense.

Lee teamed up with his comic book colleague Dan DeCarlo to produce the syndicated newspaper strip My Friend Irma, based on the radio comedy starring Marie Wilson. By the end of the decade, Lee had become dissatisfied with his career and considered quitting the field.

The first superheroes Lee and artist Jack Kirby created together were the Fantastic Four. The team's immediate popularity led Lee and Marvel's illustrators to produce a cavalcade of new titles. Again working with Kirby, Lee co-created the Hulk, Thor, Iron Man, and the X-Men.

Lee and Bill Everett created, Daredevil; and with Steve Ditko, Doctor Strange and Marvel's most successful character, Spider-Man, all of whom lived in a thoroughly shared universe. Lee and Kirby gathered several of their newly created characters together into the team title The Avengers and would revive characters from the 1940s such as the Sub-Mariner and Captain America.

Throughout the 1960s, Lee scripted, art-directed and edited most of Marvel's series, moderated the letters pages, wrote a monthly column called "Stan's Soapbox", and wrote endless promotional copy, often signing off with his trademark motto, "Excelsior!"

Following Ditko's departure from Marvel in 1966, John Romita Sr. became Lee's collaborator on The Amazing Spider-Man. Within a year, it overtook Fantastic Four to become the company's top seller. Lee and Romita's stories focused as much on the social and college lives of the characters as they did on Spider-Man's adventures.

The U. S. Department of Health, Education and Welfare had asked Lee to write a comic-book story about the dangers of drugs and Lee conceived a three-issue subplot in The Amazing Spider-Man #96–98 (cover-dated May–July 1971), in which Peter Parker's best friend becomes addicted to prescription drugs. The Comics Code Authority refused to grant its seal because the stories depicted drug use; the anti-drug context was considered irrelevant. With Goodman's cooperation and confident that the original government request would give him credibility, Lee had the story published without the seal. The comics sold well and Marvel won praise for its socially conscious efforts. The CCA subsequently loosened the Code to permit negative depictions of drugs, among other new freedoms.

In 1972, Lee stopped writing monthly comic books to assume the role of publisher. His final issue of The Amazing Spider-Man was #110 (July 1972) and his last Fantastic Four was #125 (August 1972).

Lee and John Buscema produced the first issue of The Savage She-Hulk (February 1980), which introduced the female cousin of the Hulk, and crafted a Silver Surfer story for Epic Illustrated #1 (Spring 1980).

He moved to California in 1981 to develop Marvel's TV and movie properties. He was an executive producer for, and made cameo appearances in Marvel film adaptations and other movies.

Lee stepped away from regular duties at Marvel in the 1990s, though he continued to receive an annual salary of $1 million as chairman emeritus.

In 1998 he and Peter Paul began a new Internet-based superhero creation, production, and marketing studio, Stan Lee Media. It grew to 165 people and went public through a reverse merger structured by investment banker Stan Medley in 1999.

Near the end of 2000, investigators discovered illegal stock manipulation by Paul and corporate officer Stephan Gordon. Stan Lee Media filed for Chapter 11 bankruptcy protection in February 2001. Paul was extradited to the U.S. from Brazil and pleaded guilty to violating SEC Rule 10b-5 in connection with trading his stock in Stan Lee Media. Lee was never implicated in the scheme.

DC Comics released its first work written by Lee, the Just Imagine... series, in which Lee re-imagined the DC superheroes Superman, Batman, Wonder Woman, Green Lantern, and the Flash.

In 2001, Lee, Gill Champion, and Arthur Lieberman formed POW! (Purveyors of Wonder) Entertainment to develop film, television and video game properties.Lee created the risqué animated superhero series Stripperella for Spike TV.In 2004, POW! Entertainment went public through a reverse merger again structured by investment banker Stan Medley.

From July 2006 until September 2007 Lee hosted, co-created, executive-produced, and judged the reality television game show competition Who Wants to Be a Superhero? on the Sci-Fi Channel.

The 2008 National Arts Medal was awarded to Stan Lee and presented in the East Room ceremony by President Bush in 2008. Lee was honored as one of America's most prolific storytellers "for his pioneering work, recreating the American comic books.

The Stan Lee Foundation was founded in 2010 to focus on literacy, education, and the arts. Its stated goals include supporting programs and ideas that improve access to literacy resources, as well as promoting diversity, national literacy, culture and the arts.

In October 2011, Lee announced he would partner with 1821 Comics on a multimedia imprint for children, Stan Lee's Kids Universe, a move he said addressed the lack of comic books targeted for that demographic; and that he was collaborating with the company on its futuristic graphic novel Romeo & Juliet: The War, by writer Max Work and artist Skan Srisuwan.

In September 2012, Lee underwent an operation to insert a pacemaker, which required cancelling planned appearances at conventions. Lee eventually retired from convention appearances by 2017.

At the 2016 Comic-Con International, Lee introduced his digital graphic novel Stan Lee's God Woke, with text originally written as a poem he presented at Carnegie Hall in 1972. The print-book version won the 2017 Independent Publisher Book Awards' Outstanding Books of the Year Independent Voice Award.

On July 6, 2017, his wife of 69 years, Joan, died of complications from a stroke. She was 95 years old.

Lee died on November 12, 2018, six weeks before his 96th birthday at Cedars-Sinai Medical Center in Los Angeles, California, after being rushed there in a medical emergency earlier in the day.His body was cremated and his ashes were given to his daughter.