In November 2001, Stan Lee formed POW! Entertainment, LLC, a Delaware limited liability company, with Gill Champion and Arthur Lieberman. POW set up their offices at Metro-Goldwyn-Mayer's headquarters in Santa Monica, California as a first look deal was negotiated in April 2002 by Lieberman with MGM and Cheyenne Enterprises, Bruce Willis's and producer Arnold Rifkin's production company.

Lee created the risqué animated superhero series Stripperella for Spike TV's The Strip animated block which premiered on June 26, 2003. POW! also had a dozen additional feature and television production agreements by July. Three of the films were in preproduction: Nightbird, The Femizons then with writers Cary Solomon and Chuck Konzelman and The Double Man, then under development by Training Day director Antoine Fuqua. A production agreement was signed by POW! and Idiom Films for Forever Man, an avenging hero type with a twist. Meanwhile, the company signed with DIC Entertainment on a TV series production deal starting with Stan Lee's Secret Super Six, about teens with alien superpowers who are taught by Lee about humanity. The in-development Hefs Superbunnies animated superhero series was announced by Lee at Comic-Con 2003, which would feature a villain fighting Hugh Hefner and his playmates.

The separate corporation, POW! Entertainment, Inc., is a holding company created so as to have publicly traded stock. This corporation originated as the Delaware corporation Megatek Legacy Systems, Inc., formed August 17, 1998; this became Alta Pacific Minerals, Inc. in 1999, and Arturion Entertainment, Inc. in 2002 By 2004, Arturion' stockholder were Media Dynamics, Inc., owned by Valerie Barth, controlling stockholder, and minority stockholder, UltraVision Inc., owned by Ron Sandman. Arturion was a public shell corporation that was used to acquire POW! on May 5, 2004, with POW! members receiving Arturion shares to take it public on the over-the-counter market "Pink Sheets" in a reverse merger. Arturion changed its name to POW! Entertainment, Inc. Media Dynamics invested $500,000 for 769,250 shares with a subscription for additional shares for $650,000.

In August 2004, he announced a superhero program that would feature Ringo Starr, the former Beatle, as the lead carácter. Additionally, in August of that year, Lee announced the launch of Stan Lee's Sunday Comics. 

In May 2004, IDT Entertainment purchased a minority share in POW Entertainment in an agreement for exclusive distribution rights to POW's animated DVD properties and a joint development of six cartoon films. In 2005, the company announced that another animated film that would feature the voice of Ringo Starr. Also in early 2005, the company formed a strategic partnership to develop a new mobile channel with mobile-streaming pioneer Vidiator, through Vidiator's mobile streaming technology. In 2006, this resulted in an agreement with Sprint Nextel Corp. where the Stan Lee's POW! Mobile Channel is officially listed as Sprint's Channel 70.[1The channel includes mobisodes with Stripperella, The Accuser and The Drifter.[citation needed]

In 2004, an agreement with Andrew Stevens Entertainment Group and Jeff Franklin of FWE Inc. indicated that POW! and Lee planned to produce three action movies for the Sci Fi Channel, which were to be aired in 2005–2006. Only one movie, Lightspeed, was completed for Sci Fi and aired July 26, 2006.

In December 2004, in a joint venture agreement with Celebrities In Action, a company formed by investment banker Stan Medley (who structured POW! Entertainment's reverse merger earlier in the year and Chris Nassif, President of Diverse Media Group, Lee was to create approximately 25 characters based on celebrities. POW! and CIA were scheduled to commence production in early spring of 2005. In February 2005, POW! Announced a second project with Celebrities In Action called The Fantasy Zone. The new franchise was to introduce a parallel universe where celebrities can go to live out their own fantasies and dreams.

POW!'s president and CEO, Gill Champion said in 2005 that Lee was creating a new superhero film, Foreverman, for Paramount Pictures in tandem with producer Robert Evans and Idiom Films, with Peter Briggs hired to collaborate with Lee on the screenplay. In 2005, Lee and Michelle Rodriguez agreed to develop a Tigress film, based on the Conan the Barbarian comic book villainess.

In 2007, POW! started a series of direct-to-DVD animated films under the Stan Lee Presents banner. The two releases were Mosaic and The Condor.

POW! and Walt Disney Studios agreed to a first-look deal in June 2007.[18] The following year, the first three titles under that deal were announced: Nick Ratchet, Blaze and Tigress, an original concept from the Conan villainess.

On June 9, 2007, a suit was brought against Lee, POW!, subsidiary QED Entertainment, and the former Stan Lee Media staff at POW!. On January 20, 2009, Judge Stephen Wilson, in Los Angeles Federal Court, ruled that Stan Lee Media had illegally transferred their assets, including the Drifter and the Accuser, to POW! in violation of a bankruptcy court order.

In April 2008, Brighton Partners and Rainmaker Animation announced a partnership with POW! to produce a CGI film series, Legion of 5. That same month, Virgin Comics announced Lee would create a line of superhero comics for that company.

On December 31, 2009, The Walt Disney Company's Catalyst Investments acquired a 10% stake in POW! for $2.5 million, coinciding with its full acquisition of Marvel Entertainment. Also, Disney's Silver Creek Pictures entered into another agreement with POW! for first-look and consulting services. 

In 2010, POW started reporting to OTC Markets Group and was moved to the Over-The-Counter QB (OTCQB) tier market from the pink sheets.[3] In February of that year, POW! partnered with A Squared Entertainment (A2) and Archie Comics to create the Stan Lee Comics print and digital line starting with the Super Seven. On August 5, the reality-television series Stan Lee's Superhumans show premiered on the cable channel History.Also that month, Super7, a toy manufacturer, sued POW! and partners over Stan Lee Comics' Super Seven. Late in the year, POW! and Boom! Studios began publishing three new comic-book series: Soldier Zero, Starborn, and The Traveler. In October, Guardian Media Entertainment, a partnership of Lee, SLG Entertainment and NHL Enterprises, created hockey-themed superheroes called "Guardians" for each of the 30 teams in the National Hockey League. The venture includes a graphic novel.

Ricco Capital and Panda Media Partners, a joint venture of POW! and Fidelis Entertainment, formed a partnership, Magic Storm Entertainment, in June 2011 to produce material for Asia. In 2011, Lee was writing a live-action musical, The Yin and Yang Battle of Tao. In October, Lee announced he would partner with 1821 Comics on a multimedia imprint for children, Stan Lee’s Kids Universe, a move that addressed the lack of comic books targeted for children. He also said he was collaborating with the company on its futuristic graphic novel Romeo & Juliet: The War, by writer Max Work and artist Skan Srisuwan. In November, POW signed an agreement with YouTube and Vuguru, Michael Eisner’s digital studio, to start a YouTube channel called Stan Lee's World of Heroes. That same month, the company signed a deal with EQAL to create and launch theRealStanLee.com, an official site for Lee.

In May 2012, Arthur Lieberman, Chief Operating Officer and Chief Counsel of POW!, died due to lung cáncer. Also in May, POW! filed suit against Valerie Barth of Media Dynamics and Ron Sandman, sole director of UltraVision Inc., for fraud and breach of contract, claiming it is owed $1.15 million for a three-million common stock subscription. Barth, Sandman and their corporations countersued. 

In March 2013, Hub Network picked up its first work from POW, "Stan Lee's Mighty 7", an animated pilot movie to be aired in early 2014.

On April 5, 2013, a joint venture that POW! owns with MKC Entertainment, SL Power Concerts, launched its military friendly Stan Lee's POW!er Concert series with country band Gloriana at the Pacific View Events Center, Camp Pendleton, along with future concerts at other military bases, and proceeds going to military affiliated charities. On June 12, POW and JADS International released the Stan Lee Signature Cologne. Legion of 5 was revealed in June to be a live action film at Sandman Studios-affiliated live action label Paralight Films in the casting stage. Arad Productions and POW! are in early development on a new superhero movie set up at Columbia Pictures as of November 2013, which is revealed in August 2014 as Apollo Rising, as it was melded with Red Queen author Victoria Aveyard's script Eternals. 

POW! formed Stan Lee Global Entertainment as a joint venture in 2014 with the Hong Kong-based investment firm, Ricco Media Investments Limited. Ricco Media was purchased by Focus Media Network Limited on August 20, 2015. POW! also announced two Chinese projects in October 2015: Realm, a superheroine movie and the first film from Stan Lee Global Entertainment, and Arch Alien, a sci-fi movie. 

Disney's second and final project under the first look deal with POW is The Zodiac Legacy book series, with the first book to be released through Disney Publishing Worldwide in January 2015. However, the first look deal agreed to in 2006 and extended in 2009 was allowed to expire as of December 31, 2014.

Digital Domain announced a joint venture company 25% owned by POW! was announced in January 2015 for development, production and international distribution of project from either owner. Also part of this deal is the creation of a virtual Stan Lee.

Stan Lee's Lucky Man was picked up in March 2015 by Sky1 to be adapted into a one-hour, 10-episode show, as a POW! co-production with Carnival Films and his first UK drama series. A second season was ordered in March 2016, as it was Sky1's highest-rated original drama program ever.