Wanting to cast a "tough kid" who had the life experience to understand the character he would portray, director Joel Schumacher chose Renfro to play the role of Mark Sway.

Renfro soon attracted a large fanbase as he continued to star in films such as The Cure, Tom and Huck, Sleepers, Apt Pupil, Bully and Ghost World.

Beginning in the late 1990s, Renfro experienced difficulties in his private life, including drug addiction and a series of arrests.

Finn had contacted various agencies that worked with youth; she was looking to cast a "tough" kid and settled on Renfro after looking at 5,000 such boys all over the United States.

The film was directed by Barry Levinson and Renfro played the younger version of co-star Brad Pitt's character.

[11] He played Leon S. Kennedy in a live-action ad for Resident Evil 2 directed by George A. Romero, which aired in Japan.

He went on to act in other films, including 2001's Ghost World, Bully, Happy Campers, Tart; 2002's American Girl; and 2005's The Jacket.

[citation needed] Renfro appeared in the first version of the music video for the 10 Years song "Wasteland";[12] his cousin, Jesse Hasek, is the band's lead singer.

[29] In June 2007, Renfro was found to have violated his probation by failing to enroll in a long-term drug treatment program.

On February 8, 2008, the Los Angeles County Coroner's office ruled his death accidental, attributing it to acute heroin/morphine intoxication.

[32][33] 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.

[40] 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.

BuzzFeed found no evidence that laws or contractual provisions had been violated on Renfro's films, but suggested that the industry had failed the actor by not ensuring that he was appropriately supervised when he was off the movie set.

[6] Fernando Altschul, the first assistant director of Apt Pupil, told BuzzFeed that he saw a 14-year-old Renfro at an on-set party where alcohol was available.

[6] During Renfro's early career, his worldliness and self-confidence caused many adults who came into contact with him to believe that he was some years older than his actual age.

Gemma Jackson, production designer on Tom and Huck, remembered Renfro as being 15 or 16 years of age during filming when he was actually 13.