Jon continued to get small parts until 1990, when he won a role in the television adaptation of Stephen King's IT. Jon played the part of "Stuttering Billy" Denbrough. He co-starred with the late John Ritter, as well as Seth Green of Buffy the Vampire Slayer fame. Later that year, Jon also was featured in the sequel to the Neverending Story, in which he played the part of Bastian. In addition to roles in television series, he also had several guest-starring roles on many series such as Blossom and Full House. Jon, in addition to working, attended public school as well.

Jon's big break in films came when he landed a part in Ladybugs, starring opposite Rodney Dangerfield. The film called for Jon to play a character who had to wear girl's clothing at the behest of Dangerfield's charachter. The film didn't do very well at he box office, but it did put Jonathan Brandis in the spotlight. In 1992, Jon starred along side action hero Chuck Norris as well as Beau Bridges in Sidekicks. This film was a more commercial success as opposed to his earlier film. Around 1993, Jon starred in his best known part, on the television series Sea Quest DSV, starring with Roy Schieder of Jaws fame.

During the next several years, Jon appeared in several movies including Fall into Darkness, Outside Providence, and A Fate Totally Worse than Death. In 2002, Jon appeared in Hart's War, which starred Bruce Willis. He also received a starring role in the independent film The Year the Trembled in 2002.