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Titus was born in Castro Valley, California to Ken Titus and Juanita C. Holmes. Christopher's parents divorced when he was a young child, and he was raised largely by his father, Ken, a judgmental, chain-smoking, hard drinker who was married six times and divorced five times. His mother, Juanita, suffered from schizophrenia and spent time in and out of mental hospitals. At four he was taken away from his father and given to his grandparents on his mother's side. His father went to kidnap him back and told the local district attorney of his plans without knowing. Rather than arrest him, the attorney gave him legal tactics he could use to get his son back which he used and eventually regained custody of Christopher.

When he was 12 he ran away from his father to live with his mother, during which he lived in her garage but he shortly moved back with his father. According to Titus in Norman Rockwell is Bleeding, Juanita was acquitted in 1986 after murdering her second husband who beat her up during Thanksgiving dinner, and committed suicide in 1994 after marrying another abusive man and being sent to therapy for hurling a Duraflame log through the window of a Missouri sheriff's office. This resulted in Titus having a nervous breakdown on his flight a week after her funeral. His father, Ken Titus, died in 2001 of cardiac arrest. Christopher dedicated his entire "Norman Rockwell is Bleeding" special and an episode of his show Titus ("The Pendulum," where Christopher is in a coma following a racecar crash and Ken [played by Stacy Keach] narrates the episode in Christopher's Neutral Space) to his late father.

Titus had problems with alcohol and drugs during adolescence until one day, while intoxicated, he fell into a bonfire at a beach party. In the morning, his friends took him to the hospital, where the doctor told him he would have died if he had inhaled the deadly hot smoke inside of the bonfire. He calls this moment his "epiphany" and began to turn his life around and get into comedy. He has a younger stepbrother named Dave Scouville

Titus married his wife Erin Carden on April 17, 1991. Their daughter, Kennie Marie Titus (named after his late father Ken) was born August 25, 2001. Three years later their son Jett Evan Titus was born on May 8, 2004. Titus filed for divorce on June 6, 2006, because of her affairs with two other men.

Titus shares custody of his two children with his ex-wife though has stated that the divorce has been "messy." Titus currently lives with his girlfriend of the last 5 years, Rachel Bradley, in California.