Renfro was born on July 25, 1982, in Knoxville, Tennessee, the son of Angela Denise Olsen (née McCrory) and Mark Renfro, a factory worker. He was raised from the age of five by his paternal grandmother, Joanne Renfro, a church secretary, after his parents divorced. He reportedly did not have a close relationship with his father. Renfro’s cousin, Jesse Hasek, is the lead singer of the band 10 Years.

When he was 10 years of age, Renfro was discovered by Mali Finn, a casting director for Joel Schumacher. He had no prior acting experience or training at the time. Finn had contacted various agencies that worked with youth; he was looking to cast a “tough” kid and settled on Renfro after looking at five thousand such boys all over the United States. At the time, Renfro had been living in a trailer park outside Knoxville with his grandmother. “I wanted a kid who understood in the marrow of his psyche what it was like to grow up too soon,” Schumacher later told The New York Times. Renfro was cast by Finn as the lead in Schumacher’s The Client. His casting was announced in May 1993, and the movie was filmed in the summer of that year. Based on the bestselling John Grisham novel, The Client became one of the top-grossing films of 1994. In 1995, Renfro won The Hollywood Reporter’s “Young Star” award, and was nominated as one of People magazine’s “Top 30 Under 30.”

In 1996, Renfro appeared in Sleepers, which was based on the novel of the same name by Lorenzo Carcaterra. The film was directed by Barry Levinson and co-starred Brad Pitt, who played the older version of Renfro’s character.

In 1998, he starred in Apt Pupil, directed by Bryan Singer. The several films he starred in that followed gained little attention, with the majority going straight to video. He played Leon S. Kennedy in a live-action ad for Resident Evil 2, which aired in Japan. Renfro went on to act in other films, including 2001’s Ghost World and Bully, 2002’s Confessions of an American Girl, and 2005’s The Jacket. He also appeared in the 2006 Law & Order: Criminal Intent episode “Watch”, and completed filming on the film The Informers.

On June 3, 1998, Renfro, then 15, and his 19-year-old cousin were arrested and charged with drug possession. He was carrying two small bags of cocaine in a cigarette box and a bag of marijuana in his sock. He entered into a plea bargain in which he agreed to random drug tests.

On August 28, 2000, Renfro and a friend attempted to steal a yacht from the Fort Lauderdale harbor. Renfro was charged with grand theft and criminal mischief; in January 2001, he was sentenced to two years’ probation and ordered to pay investigative costs and yacht repair costs. Renfro violated his probation in May 2001 when he was arrested for underage drinking. On January 14, 2002, Renfro violated his probation again and was arrested on charges of public intoxication and driving without a valid license in Knoxville. He was placed into a three-month substance abuse treatment program as a result.

Renfro had one child, a son born in 2003 in Japan, and raised there by his mother, a Japanese citizen. Prior to Renfro’s passing, the public had been unaware he had a son, and mention of him did not appear in his obituary, though his son was eventually named in the obituary of Renfro’s mother, Angela, who died in 2012.

On November 24, 2005, Renfro was charged with a misdemeanor count of driving under the influence and two counts of driving with a suspended license, leading to 10 days in jail and 18 months of alcohol education classes. He was arrested by LAPD officers on December 22, 2005, during an undercover drug sweep of Skid Row. Following that arrest, he was charged with attempted possession of heroin. A photograph showing him in handcuffs made the front page of the Los Angeles Times. Renfro admitted to a detective that he was using heroin and methadone. He pleaded guilty, was sentenced to three years’ probation, and was fined $450. In May 2006, he spent 10 days in jail for driving while under the influence and attempted heroin possession.

In June 2007, Renfro was found to have violated his probation by failing to enroll in a long-term drug treatment program. A judge warned him that if he violated probation two more times, he could be sentenced to a live-in rehabilitation program or to jail.

Following Renfro’s death in January 2008, his cousin, Jesse Hasek, stated that Renfro and his son had visited him several days earlier and that Renfro had made positive changes in his life. According to Hasek, “‘He had hit rock bottom and had come way back up'”.

Renfro was found dead on January 15, 2008, in his Los Angeles apartment. He was 25 years old. His body was returned to Tennessee, where he was buried on January 22, 2008, at Red House Cemetery in the small community of Blaine, Tennessee. On February 8, 2008, the Los Angeles County Coroner’s office ruled his death accidental, attributing it to acute heroin/morphine intoxication.

In 2012, the art magazine The Thing Quarterly reported that actor James Franco had the name “Brad” tattooed on his right shoulder in memory of Renfro. Franco also produced a limited-edition series of switchblades bearing the words “Brad Renfro” and “Forever.”

In 2018, 10 years after Renfro’s death, and again the following year, the website BuzzFeed devoted a long article to recounting his rise and descent, particularly during the 1990s while he was still a teenager. The article discussed whether the film industry’s methods of protecting the welfare of child actors during production were adequate for situations involving at-risk child actors. BuzzFeed found no evidence that laws or contractual provisions had been violated on his films, but suggested that the system had nonetheless failed the actor by not ensuring that he was appropriately supervised when he was off the movie set.