Cornelius Crane Chase was born in Lower Manhattan on October 8, 1943, and grew up in Woodstock, New York. He has an older brother, Ned Jr.

His father, Edward Tinsley "Ned" Chase (1919–2005), was a Princeton-educated Manhattan book editor and magazine writer. Chase's paternal grandfather was artist and illustrator Edward Leigh Chase, and his great-uncle was painter and teacher Frank Swift Chase. His mother, Cathalene Parker (née Browning; 1923–2005), was a concert pianist and librettist, whose father, Rear Admiral Miles Browning, served as Admiral Raymond A. Spruance's Chief of Staff on the aircraft carrier USS Enterprise at the Battle of Midway in World War II. Cathalene was adopted as a child by her stepfather, Cornelius Vanderbilt Crane, heir to The Crane Company, and took the name Catherine Crane. Her mother, also named Cathalene, was an opera singer who performed several times at Carnegie Hall.

Chase was named for his adoptive grandfather, Cornelius, while the nickname "Chevy" was bestowed by his grandmother from the medieval English ballad "The Ballad of Chevy Chase". As a descendant of the Scottish Clan Douglas, she thought the name appropriate. Chase is a 14th-generation New Yorker, and was listed in the Social Register at an early age. His mother's ancestors arrived in Manhattan starting in 1624 — among those ancestors are:
• New York City mayors Stephanus Van Cortlandt and John Johnstone
• the Dutch Schuyler family, through his ancestor Gertrude Schuyler, the wife of Stephanus Van Cortlandt
• John Morin Scott, General of the New York Militia during the American Revolution
• Anne Hutchinson, dissident Puritan preacher and healer
• Mayflower passengers and signers of the Mayflower Compact from England, John Howland, and William Brewster, the Pilgrim colonist leader and spiritual elder of the Plymouth Colony
According to his step-brother John:

[Chevy] once told me that people who defined themselves in terms of their ancestry were like potatoes—the best parts of them were underground. He disdained the pretension of his mother's side of the family, as embodied by her mother, Cattie.
As a child, Chase vacationed at Castle Hill, the Cranes' summer estate in Ipswich, Massachusetts. Chase's parents divorced when he was four; his father remarried into the Folgers coffee family, and his mother remarried twice. He has stated that he grew up in an upper middle class environment and that his adoptive maternal grandfather did not bequeath any assets to Chase's mother when he died. In a 2007 biography, Chase stated that he was physically and psychologically abused as a child by his mother and stepfather, Dr. John Cederquist, a psychoanalyst. In that biography, he said, "I lived in fear all the time, deathly fear." Abuse he was subjected to as a child included being awoken in the middle of the night by his mother to be slapped repeatedly across the face, lashes to the backs of his legs, punches to the head by his stepfather, and being locked in a bedroom closet for hours. As a punishment for being su…

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Chase married Susan Hewitt in New York City on February 23, 1973. They divorced on February 1, 1976. His second marriage, to Jacqueline Carlin, was formalized on December 4, 1976, and ended in divorce on November 14, 1980; they had no children.

Chase resided in Pacific Palisades, Los Angeles from 1980 until 1995 in a Tudor-style home. He was the Honorary Mayor of Pacific Palisades between 1986 and 1988.

He married his third wife, Jayni Luke, in Pacific Palisades on June 19, 1982. He and Luke have three daughters, Cydney, Caley, and Emily. The couple reside in Bedford, New York.
In 1986, Chase was admitted to the Betty Ford Center for treatment of a prescription painkiller addiction. His use began after he experienced ongoing back pain related to the pratfalls he took during his Saturday Night Live appearances. In 2010, he said that his drug abuse had been "low level."

He entered the Hazelden Clinic in September 2016 to receive treatment for alcoholism.
An active environmentalist and philanthropist, Chase is a political liberal. He campaigned for Bill Clinton in the 1990s, and for John Kerry in the 2004 presidential election.

In 2004, he mocked President George W. Bush during a speech at a People for the American Way benefit at the John F. Kennedy Center for the Performing Arts, where he referred to Bush as an "uneducated, real lying schmuck" and a "dumb fuck", which upset the organizers and the crowd, leading Norman Lear to categorize the statements as "utterly untoward."
While filming an episode of Saturday Night Live in 1978, Chase got into a fistfight with Bill Murray in John Belushi's dressing room. Murray and Chase's backstage brawl took place when Chase returned to host the show after his exit as a full-time cast member in 1976. Murray had reportedly made a derogatory comment about Chase's troubled marriage to Jacqueline Carlin, leading Chase to criticize Murray's physical appearance. SNL cast members Jane Curtin, Laraine Newman, and Gilda Radner witnessed the incident.

In a talk show appearance in 2021, Newman noted of the altercation, "it was very sad and painful and awful". She went on to say, "I think they both knew the one thing that they could say to one another that would hurt the most and that's what I think incited it." Chase and Murray would later reconcile to star together in Caddyshack in 1980.

• I'm Chevy Chase...and You're Not (The Authorized Biography) by Rena Fruchter. Virgin Books, 2007. ISBN 1-85227-346-1.
• Who's Who in Comedy by Ronald L. Smith. Pp. 102–103. New York: Facts on File, 1992. ISBN 0-8160-2338-7.
• Live from New York: An Uncensored History of Saturday Night Live by Tom Shales and James Andrew Miller. Back Bay Books.