During his first year, he created a series of short cartoons featuring a character named No Neck Joe, which were picked up by Spike and Mike's Sick and Twisted Festival of Animation.

[7][8] In 1993, McCracken was hired by Hanna-Barbera Cartoons as an art director on the Turner Broadcasting System series 2 Stupid Dogs, alongside Tartakovsky.

[10] While McCracken was at Hanna-Barbera, studio president Fred Seibert began a new project: an animation incubator consisting of 48 new cartoons running approximately seven minutes each.

McCracken's Powerpuff Girls was the fourth cartoon to be greenlit a full series, which premiered on November 18, 1998, with the final episode airing on March 25, 2005.

[22] After Wander Over Yonder was cancelled, McCracken pitched a new show to Disney, based on his 2009 comic strip The Kid from Planet Earth.

[31][32] On July 18, 2022, it was announced that McCracken began developing reboots of The Powerpuff Girls and Foster's Home for Imaginary Friends at Hanna-Barbera Studios Europe.

[35] Since his early years of career, McCracken has chosen to design characters in a simplistic way (as opposed to the realism of Warner Bros. or Disney feature films) because it is more practical for television production, as money and time limits what the animators can do.

To mention some: 1960s Batman, Underdog and Rocky and Bullwinkle in The Powerpuff Girls,[38] The Muppet Show and SpongeBob SquarePants in Foster's Home for Imaginary Friends (which also has a visual style inspired by 60s psychedelia),[39][40] Yellow Submarine and Looney Tunes in Wander Over Yonder,[41] and Dennis the Menace and The Adventures of Tintin in Kid Cosmic.

[37] For example, Kid Cosmic is about a group of "punk rock" characters who "may not have the skill or the talent, but they have the determination and conviction" to create a superhero team.

[44] Although the Powerpuff Girls have been widely regarded as feminist icons, McCracken has claimed that the real background for their creation was finding "a fun idea" or "a cool concept".