Brandis was born in Danbury, Connecticut. He was the only child of Mary, a teacher and personal manager, and Gregory Brandis, a food distributor and firefighter. He began his career as a child model at the age of 4, and began acting in television commercials.  At the age of six, Brandis won the role of Kevin Buchanan on the soap opera One Life to Live. He moved to Los Angeles with his family at age nine, and made guest appearances on shows such as L.A. Law, Who’s the Boss?, Murder, She Wrote, The Wonder Years, Full House and Kate & Allie. At the age of fourteen, he received his first starring role, as Bastian Bux in The NeverEnding Story II: The Next Chapter. That same year, Brandis played the young “Stuttering Bill” Denbrough, the main protagonist in the 1990 film Stephen King’s It, alongside Tim Curry, based on the epic horror novel of the same name. Brandis’ performance in the film was lauded by critics and audiences. Brandis then appeared in Sidekicks, costarring Chuck Norris, and in Ladybugs, with actor/comedian Rodney Dangerfield.

Around the age of 17, Brandis landed one of his best-known roles, as scientific prodigy Lucas Wolenczak in Steven Spielberg’s futuristic science fiction series seaQuest DSV. The role propelled him into teen idol status. At the height of his popularity, Brandis received approximately 4,000 fan letters a week and had to be escorted onto the set of seaQuest DSV by three studio security guards because of the many female fans present. During his stint on seaQuest DSV, he co-wrote and produced an episode of the series titled “The Siamese Dream”. He also voiced Mozenrath, an evil young sorcerer and necromancer, in Disney’s animated series Aladdin. After seaQuest DSV was canceled in 1996, Brandis appeared in the television film Her Last Chance, starring Kellie Martin. His next role was in the television film Born Free: A New Adventure. Shot in South Africa, the film also starred Chris Noth as Brandis’s character’s father. He continued his career in supporting roles in Outside Providence (1999), and Ride with the Devil (1999). In 2000, he costarred in Bad Girls from Valley High, which, because of distribution problems, was not released until 2005. In 2002, Brandis had a small role in Hart’s War (2002). The following year, he was cast in 111 Gramercy Park, a pilot for ABC that was not picked up by the network. He made his final onscreen appearance in Puerto Vallarta Squeeze, starring Harvey Keitel and Scott Glenn. That film was also released after his death. In addition to acting, Brandis directed several independent films and authored screenplays. He also produced and directed the short film The Slainville Boys shortly before his death.

Shortly before midnight on November 11, 2003, Brandis hanged himself in the hallway of his Los Angeles apartment building. He was discovered by friends who called paramedics who transported the actor to Cedars-Sinai Medical Center. Brandis died there on the afternoon of November 12 from injuries he sustained from the hanging. Brandis did not leave a suicide note. After his death, friends said that he was depressed about his waning career, which had continued to decline in the final years of his life. He was also reportedly disappointed when his appearance in the 2002 war drama Hart’s War, a role he had hoped would revive his career, was significantly reduced in the film’s final cut. One friend admitted to People magazine that Brandis had begun drinking heavily and had said that he intended to kill himself. Paul Petersen, a former child actor and president of A Minor Consideration—an organization that deals with issues affecting child actors—stated: “Speculations as to the underlying cause of this tragedy are exactly that: speculations. It serves no purpose to leap to conclusions for none of us will really know what led Jonathan to his decision to take his life.”