Chambers was born in Springfield, Ohio, the son of Pam and John Chambers. He has a fraternal twin brother named Jason, one older brother John Jr. (Chip), and two older sisters, Mia and Susan. He and his twin brother visited hospitals often as children due to frequent bouts with pneumonia. He attended Southeastern High School in South Charleston, Ohio, and later Springfield Clark JVS.
In 1993, he married Keisha Chambers, a former model agency booker; they have five children together: Isabella (b. December 1994), twins Maya and Kaila (b. June 1997), Eva (b. March 1999) and Jackson (b. January 2002). His wife and children have recently moved from their home in a suburb just outside of New York City to Los Angeles. In late January 2008, Chambers admitted that he suffered from a biological sleep disorder. The actor checked himself into Los Angeles's UCLA Medical Center to treat exhaustion due to the sleep disorder after a period of getting only two hours of sleep each week.