It was co-written and directed by series' creator Craig McCracken (in his feature-length directorial debut), co-written by Charlie Bean, Lauren Faust, Paul Rudish, and Don Shank, and stars the regular television cast of Catherine Cavadini, Tara Strong, E. G. Daily, Roger L. Jackson, Tom Kane, Tom Kenny, Jennifer Hale, and Jennifer Martin.

The film serves as a prequel to the series, and tells the origin story of how the Powerpuff Girls were created and came to be the defenders of Townsville and how Mojo Jojo became a supervillain.

Suddenly, a chimpanzee named Jojo, who was the Professor's destructive laboratory assistant until gaining superintelligence due to the Chemical X explosion mutating his brain, rescues the trio.

According to Cartoon Network executives, it was also meant to "spark sales of DVDs and home videos, pack in crowds overseas and set kids scrambling to buy cartoon-themed merchandise".

[6] Jim Samples, executive vice president and general manager of the network, saw the year 2002 as a good opportunity to bring the show to the big screen, given the success of family features such as Disney's Lilo & Stitch and the live-action adaptation of Scooby-Doo.

By the time we finished, there was a regime change at CN and the new heads of the network were upset we didn't make a poppy, colorful kids movie [...] This was when they first had the idea that they wanted to try producing animation for older audiences, Samurai Jack was a part of this thinking as well.

All work done overseas was then shipped to Los Angeles, where the main crew put every single shot together digitally at the recently opened Cartoon Network Studios.

According to McCracken, 49 half-hour episodes of the TV series had been made up to that point, but production on the show went on hiatus to focus on the making of the movie.

[13] By February 2002, the film was already being promoted on Cartoon Network's official website, where details about the "Be an Artist" contest were available, prompting fans in the United States under the age of 18 to send their drawings in the hopes of having it appear in a scene from the movie.

[21] In July 17, DC published the film's official comic adaptation, written by Amy Rogers and illustrated by Phil Moy, Christopher Cook and Mike DeCarlo.

[25] A premiere screening was held by Warner Bros. in Century City, California on June 22, 2002, which a part of the film's cast and crew attended, as well as celebrities such as Melissa Gilbert, Danny Bonaduce, Christine Lahti, Harry Hamlin, and Lisa Renee Foiles.

[30] The Region 2 DVD release presents the film in its original widescreen aspect ratio, but omits the audio commentary and bonus features, and is also in PAL format.

[34] Bob Longino of the Atlanta Journal-Constitution praised the film, saying that "the intricate drawings emanate 1950s futuristic pizazz like a David Hockney scenescape", and that the script is both "sinfully cynical and aw-shucks sweet".

[36] Virginia Heffernan of The New York Times said that "the movie is cute [...] but its violent, snickering style is pure Americana", and that it evokes the "outlandish classic" look of McCracken's inspirations.

[37] Ben Nuckols wrote for Associated Press that the protagonists' big eyes were the "only remarkable thing", which he considered "a shame, because the girls are delightful and the movie is skillfully made".

[42] Dan Via, writing for The Washington Post, said that "even with its flaws, The Powerpuff Girls Movie offers dramatic pacing, cleverness and charm that are hard to come by in the summertime multiplex", ranging from moments of "epic stillness to the crash-bang-kapow flash of the action sequences".

[44] Marc Savlov of The Austin Chronicle gave the film 3 and a half stars out of 5, describing it as "retro fun that contains a serious self-empowerment message for little girls and little boys alike", as well as "brilliant, wacky, and utterly charming fluff".

[45] In a review for the newspaper Riverfront Times, Gregory Weinkauf said that the film's exploration of the girls' emotions during the asteroid scene was "a brilliant sequence" before the "blaze of chaotic action" in the third act.

However, he was critical about the film's "bizarre anal sensibilities" (e.g. "cheeky shots of monkey butts — electroshocks slithering up into them, turd-bombs plopping out of them") and what he deemed as a "psychosexual fodder", with the Mayor having a "pickle fetish" and Sara Bellum's "voluptuous curves [that] fill the frame but whose actual head and identity as a mature woman are curiously omitted.

[47][48] The Catholic Bishops Conference of the Philippines (CBCP) gave the film a similarly negative review, labelling it as "disturbing", further opining that the movie was nothing but a "saturation of violent acts carried out with a fierce vengeance.

[8] In early 2003, the Online Film Critics Society released its list of the Top 100 Animated Features of All Time, where The Powerpuff Girls Movie was placed at number 86.

[55] However, Mekeisha Madden from The News Tribune noted that it was facing a strong competition against films like Scooby Doo, Lilo & Stitch, and Hey Arnold!

[56] The movie only earned $6.1 million over its first five days of release, ranking ninth at the North American box office due to competition with Men in Black II.

[57] Jim Samples, Cartoon Network's general manager at the time, said that these numbers were a "big disappointment", but still had hope that the movie would do better overseas and via DVD sales.

[2] Mike Lazzo, former senior vice president of Cartoon Network's Adult Swim, said that the movie flopped due to a bad combination of "business" (as for when and how it was released) and "creative" (with it being "just good" instead of "genius").