He made his TV debut as an extra in "Against the Wall", a 1994 HBO movie filmed in Tennessee, and later had a small role in the 1998 Alex Haley miniseries "Mama Flora's Family" (CBS). Qualls followed up with a supporting role in the curious teen horror feature "Cherry Falls", which was shot prior to his breakthrough in "Road Trip" but was released the following fall. His work in "Road Trip" proved far more memorable, with Qualls' portrayal of the awkward and inexperienced Kyle showcasing the actor's likability as well as his precise comic timing. Kyle's fearlessness in humiliating situations was rendered perfectly by the actor, pointing at the character's innocence without a trace of actorly arrogance. The performer also managed to balance "Road Trip"'s often broad situations with an intuitive and natural performance. Qualls impressed in the role, and proved a fresh face but not an amateur, displaying a proficiency on screen that rivaled that of co-star Breckin Meyer, an actor with dozens more roles to his credit. His talent and unusual, unforgettable looks could offer the young performer an extensive career as a character player.

After his breakout role, Qualls played variations on his lovable geek in films such as "Comic Book Villians" (2002), "Big Trouble" (2002), "The New Guy" (2002) and "The Core" (2003). Qualls then delivered an exceptionally winning performance as Shelby, the church organist-turned-rap-producer in the acclaimed indie "Hustle & Flow" (2005).