Following the name change to The Powerpuff Girls, McCracken submitted his student film to Cartoon Network, who aired the series' refined pilot, "Meat Fuzzy Lumpkins", in its animation showcase program World Premiere Toons on February 20, 1995, along with its follow-up, "Crime 101", on January 28, 1996.

The show revolves around the adventures of three kindergarten-aged girls with an array of various superpowers: Blossom (pink), Bubbles (blue), and Buttercup (green).

The plot of an episode is usually some humorous variation of standard superhero and tokusatsu shows, with the girls using their powers to defend their town from villains and giant monsters.

In addition, the girls have to deal with the normal issues that young children face, such as sibling rivalries, loose teeth,[8] personal hygiene,[9] going to school, bed wetting,[10] or dependence on a security blanket.

[15] The three girls all have abnormally large eyes inspired by Margaret Keane's art,[16] and stubby arms and legs, and lack of noses, ears, fingers, flat feet, toes, and necks.

In June 1991, he drew three girls with large eyes, visually inspired by the paintings of Margaret Keane,[16] on a small sheet of orange construction paper as a birthday card design for his brother.

McCracken explained that Cartoon Network executives believed no one would make a children's show with the word "ass" in it, so the title changed to The Powerpuff Girls and the "can of whoopass" was renamed "Chemical X".

[5] McCracken's new short, titled "The Powerpuff Girls in: Meat Fuzzy Lumpkins", aired as part the network's World Premiere Toon-In on February 20, 1995.

Veteran ABC announcer Ernie Anderson, who narrated the pilot episodes and died of cancer in 1997, was replaced by Tom Kenny when it became a series.

McCracken said that the show did not go through a large development process, but he was advised to change the name of the three main characters to Pink, Blue and Green, since the network executives found it hard to differentiate them by Blossom, Bubbles and Buttercup.

[33] By the end of 2000, merchandising based on the series encompassed a whole variety of products, including T-shirts, toys, video games, lunchboxes, and dishware.

[15] Concerning the show's success, Craig McCracken has stated, "I thought it would get on Cartoon Network and college kids would watch it and there would be a few random T-shirts out there in the rave scene or in record shops.

[38] In August 2008, McCracken revealed on his DeviantArt account, as had been announced in that year's Comic Con, that he was working with Cartoon Network on a new half-hour The Powerpuff Girls special to celebrate the series' tenth anniversary.

[43][44] Former Beatle Ringo Starr promoted the special on Cartoon Network singing a new original song "I Wish I Was a Powerpuff Girl" with previews leading up to the airdate.

[48] Common Sense Media gave the special 3/5 stars citing the "tasteful update of the original animation style" however recommends it for older kids around the age of 7.

"[51] In a 2000 Entertainment Weekly review, Marc Bernardin complimented the show on its "spot-on pop-culture acumen" and "unparalleled sense of fun", giving it a warm welcome from earlier "lame" superhero cartoons that he grew up with.

[52] Peter Marks of The New York Times noted the show's use of adult humor and pop culture references, declaring it "the sort of playful satire that can appeal as much to a viewer of 37 as 7.

[57][58] The Powerpuff Girls were often compared to the likes of Sailor Moon, Lara Croft, and Buffy the Vampire Slayer, who are also strong and heroic female leads.

[60][61] Terrence Briggs of Animation World Network noted that, "at the very least, Powerpuff Girls works as an interesting comic deviation from the more sexual presences" of other fictional heroines.

[86] It features junior high school students Momoko Akatsutsumi (Hyper Blossom), Miyako Gotokuji (Rolling Bubbles), and Kaoru Matsubara (Powered Buttercup) as the three heroes.

"[88] Delta Express promoted the series by having a Boeing 737-232 jet painted with a special livery featuring the characters Blossom, Bubbles, and Buttercup on its exterior.

According to Variety, it would depict Blossom, Bubbles and Buttercup as "disillusioned twentysomethings" resentful at losing their childhood to fighting crime and faced with the choice of reuniting "when the world needs them more than ever."

[94] Genndy Tartakovsky, who directed and produced several episodes of the original show, also expressed a similar sentiment, suggesting that the idea was "strong" and could work if there's "good people attached to it".

[102] On April 9, Robyn Lively was cast as Sara Bellum and Tom Kenny was confirmed to be reprising his role as the Narrator from the original series.

[112] The array of products was so extensive in 2002 that, according to Janan Sheria of the Dayton Daily News, even people without cable television could recognize the Powerpuff Girls.

[117] A set of six kids' meal toys was available as part of an April 2001 Dairy Queen promotion, which also included a sweepstakes offering the Powerpuff Girls VHS Boogie Frights.

[120] In the United Kingdom the characters of Buttercup and Mojo Jojo were given away in Kellogg's cereal boxes as part of the Cartoon Network Wobble Heads in 2003.

In 2014, that company published a variant cover which showed aged-up versions of Powerpuff Girls with breasts and dressed in latex.

The cover was designed by an artist working for Cartoon Network who was "thinking of it more along the lines of 'female empowerment' than the kind of thing you guys are talking about".

The first, titled Heroes & Villains, features original songs about the Powerpuff Girls characters by a number of artists, including the new wave group Devo, Bis, The Apples in Stereo and Frank Black.