In 1992, Silberling directed episodes of short-lived Fox sitcom "Great Scott", also serving as supervising producer. He later helmed episodes of "Brooklyn Bridge" for Gary David Goldberg, which caught the attention of Steven Spielberg who, as executive producer, hired him to direct "Casper" (1995). The result was a hit film that grossed more than $100 million domestically, propelling the director to the top of the A-list. He followed up with "City of Angels" (1998), loosely inspired by Wim Wenders' "Wings of Desire" (1987). The story focused on the romance between an angel (Nicolas Cage) and the woman (Meg Ryan) he was sent to watch over.

In 1989, Silberling and young actress Rebecca Schaeffer were romantically involved when she was murdered by a fanatic admirer. Silberling hosted a tearful memorial service held at the Warners Ranch, then later married actress Amy Brenneman, whom he met on the set of "NYPD Blue". Together, they founded the Cornerstone Theatre Co. in Los Angeles and in 1999, Brenneman created and starred in the hit series "Judging Amy", which Siberling directed.

In 2002, Silberling produced and directed his first script, "Moonlight Mile." This deeply personal drama was Silberling's response to the tragedy of Schaeffer's death. "Moonlight Mile" is the story of a young man (Jake Gyllenhaal) develops a relationship with the parents of his deceased fiancé. The script went to all the studios before it was bought by Disney—studios were wary of such a personal story, or as Silberling commented: "There is such a fear of any story that has death as a backdrop, even as a catalyst.” Next, Silberling directed “Lemony Snicket’s A Series of Unfortunate Events” (2004), the Jim Carrey vehicle based on the series of popular children’s books.