In 1993, McCracken was tapped by Hanna-Barbera Cartoons to be an art director on the Turner Broadcasting System series 2 Stupid Dogs, where he would also work with Tartakovsky. 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. Dubbed What a Cartoon!, it motivated McCracken to further develop his Whoopass Girls! creation, renaming it The Powerpuff Girls in the process. His new pilot, “The Powerpuff Girls in: Meat Fuzzy Lumkins”, premiered on February 20, 1995, on Cartoon Network’s World Premiere Toon-In, and a second short, “Crime 101”, followed on January 28, 1996. The first short to be picked up by the network was Tartakovsky’s Dexter’s Laboratory, which McCracken would contribute to in early seasons. McCracken’s Powerpuff 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. The show soon became a hit and has won both Emmy and Annie awards. In 2002, McCracken directed The Powerpuff Girls Movie, a prequel to his series. The film received generally positive reviews but was a box office failure. McCracken left The Powerpuff Girls after four seasons, focusing on his next project, Foster’s Home for Imaginary Friends. It premiered with the 90-minute television special “House of Bloo’s” on August 13, 2004, on Cartoon Network. He developed the series with wife Lauren Faust and Mike Moon. The show ran for six seasons, all directed by McCracken, and concluded on May 3, 2009. It also won Emmy and Annie awards.

McCracken began drawing at an early age. After he graduated from California High School in Whittier, California, he attended the California Institute of the Arts (CalArts), where he honed his animation skills and met his classmate Genndy Tartakovsky, with whom he would occasionally collaborate throughout his career. 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. While at CalArts, he also created a short entitled Whoopass Stew!, which would later become the basis for The Powerpuff Girls. McCracken married animator Lauren Faust on March 13, 2004. Faust took maternity leave in mid-2016 to take care of their newborn daughter.

In April 2008, he became executive producer of a new Cartoon Network showcase project called The Cartoonstitute. After 15 years of employment, he resigned from Cartoon Network and created Wander Over Yonder for Disney Television Animation and the Disney Channel in 2013. He is currently at Netflix creating and producing the animated series Kid Cosmic, set to premiere in 2021,.