He was discovered at age 10 by director Joel Schumacher and was cast in the motion picture The Client (1994).
For Disney, he played Huck Finn in the 1995 comedy Tom and Huck.
Renfro won The Hollywood Reporter's Young Star Award in 1995 and was nominated as one of People magazine's "Top 30 Under 30," though addiction problems in his teens and early 20s led to several police arrests and hampered his career.
Renfro was found dead on January 15, 2008 in his Los Angeles apartment at the age of 25. On February 8, 2008, the Los Angeles County Coroner's office ruled that Renfro's death was accidental, attributing it to acute heroin/morphineintoxication. His body was returned to Tennessee, where he was buried on January 22, 2008 north of Knoxville, at Red House Cemetery in the small community of Blaine.
Seventeen days after Renfro's death, his grandmother Joanne—who had accompanied him regularly during his early acting career—died at her home at the age of 76. Local officials stated that she died of natural causes.