2000 proved to be Muniz's breakthrough year, with his regular series and feature film starring debuts coming only weeks apart. On television, he played Malcolm, a harried nine-year-old with a 165 IQ who is dealing with the inane day to day struggles in his loving but unorthodox family while navigating the brutal hallways of elementary school on Fox's refreshingly frank sitcom "Malcolm in the Middle". While the entire cast was made up of excellent performers portraying wacky yet likable characters, it was Muniz's Malcolm who guided the viewer through the chaos. On the big screen, he starred in "My Dog Skip", a poignant and charming World War II set tale of a boy and his dog, based on Willie Morris' personal memoir. His portrayal imparted Willie's dreams and anxieties with skill and sophistication. Muniz effectively and appropriately reined in the shy character's playfulness around peers, and imparted the pathos of the disappointed yet idolizing attitude for his emotionally distant father (Kevin Bacon). The actor doesn't settle for the easy way out, simply employing sad puppy dog eyes to show emotion. He assuages broad characterization with a heartfelt performance that rings especially true. While only in his early teens, Muniz already had displayed enviable versatility, handling the histrionics of the perpetually outraged, camera-addressing cynical young Malcolm as well as the touching and understated struggle of the wise but innocent Willie. Later in 2000, he was featured in the Disney Channel original film "Miracle in Lane 2", playing a wheelchair-bound teen who, through determination and familial support, participates in a soapbox derby.
In 2002, he had his first big screen lead since his TV success in the children's comedy "Big Fat Liar" and undertook a featured role in the the period drama "Deuces Wild." Next up, Munitz starred as a boy who is trained to perform special operations for the government in the teen hit "Agent Cody Banks" (2003), which he followed up with an instant sequel, "Agent Cody Banks 2: Destination London" (2004). The actor also provided the voice of the zebra who wants to be a racehorse in the children's comedy "Racing Stripes" (2005).