Madio was born as one of seven children in his family. At the age of 15, he had his first audition in Steven Spielberg's 1991 film Hook. He landed the role of "Don't Ask", one of the Lost Boys. Among the cast of Hook was Academy Award winner Dustin Hoffman, who had been cast as the villainous Captain Hook. Hoffman took notice of Madio and had him cast as his character's son in the 1992 comedy Hero.
He later appeared alongside Leonardo DiCaprio in the 1995 film The Basketball Diaries as a teenage drug addict. In 1997 Madio landed a regular role on the teen sitcom USA High where he played funny-man Bobby Lazzerini during the show's first season.
He has played lead roles in television series including miniseries Band of Brothers, in which he portrayed Frank Perconte. Madio contacted Perconte to develop ideas on how to play the real-life sergeant as well as to understand Perconte's background and history. In 2003 Madio was cast in a main role of Mike Powell on the short-lived CBS courtroom drama Queens Supreme.
More recently, Madio has been focused on voice-acting and acting in independent films. He also made a 2011 guest appearance on an episode of the new TV Land comedy series The Exes.
