Sinofsky was born to a Jewish family in Boston, Massachusetts. He graduated from the Tisch School of the Arts of New York University in 1978.

Sinofsky began his career at Maysles Films. As Senior Editor at the company, he worked on commercials and feature films until 1991, when he and Joe Berlinger formed their own production company, Creative Thinking International. They jointly produced, edited and directed documentary films which have appeared on over 50 critics choice lists, including Brother's Keeper (1992), the Paradise Lost trilogy (1996, 2004, 2011), Hollywood High (2003) and Some Kind of Monster (2004).

The first movie Sinofsky directed, in 1992, was the documentary Brother's Keeper, which tells the story of Delbart Ward, an elderly man in Munnsville, New York, who was charged with second-degree murder following the death of his brother william. Chicago Sun-Times film critic Roger Ebert, in his review of the movie, called it "an extraordinary documentary about what happened next, as a town banded together to stop what folks saw as a miscarriage of justice."

Sinofsky won a Directors Guild of America Award and two Emmys, one for the first film in the Paradise Lost trilogy, The Child Murders at Robin Hood Hills. He was nominated for an Academy Award for the third film in the trilogy, Purgatory, in 2011.

Sinofsky died on February 21, 2015 at the age of 58, from diabetes-related complications. The band Metallica paid tribute to him as a "courageous man with deep empathy and wisdom who wasn't afraid to dig deep to tell the story." Berlinger wrote that Sinofsky's "humanity is on every frame of the films that he leaves behind."

The 2016 film Tony Robbins: I Am Not Your Guru is dedicated to his memory.

The 2018 documentary “May It Last: A Portrait of the Avett Brothers” [1] is also dedicated to his memory.