Quaid was born in Houston, Texas to Juanita Bonniedale "Nita", a real estate agent,and William Rudy Quaid, an electrician. Quaid has Irish and Cajun ancestry. He attended Pershing Middle School (Houston). He studied drama at Bellaire High School in Bellaire, Texas and later in college, at the University of Houston, under drama coach Cecil Pickett.

After his brother, actor Randy Quaid, was nominated for an Academy Award for his role in The Last Detail, he dropped out of the University of Houston before graduating and moved to Los Angeles, California, to pursue an acting career of his own. He initially had trouble finding work but began to gain notice when he appeared in Breaking Away (1979) and earned good reviews for his role in The Right Stuff (1983). Known for his famous grin, Quaid is a versatile actor, performing in both comedic and dramatic roles.

Quaid's career lost steam in late 1980s/early 1990s, after he fought and kicked a painful cocaine addiction. However, he continued to prove his worth in a variety of films such as a memorable performance as Doc Holliday in Wyatt Earp (1994) and has experienced a resurgence in popularity since the late nineties.

Aside from acting, Quaid is a musician and plays with his band the Sharks. Quaid also has a pilot's license and is a scratch golfer and, in 2005, was named as the top golfer among the "Hollywood set" by Golf Digest. He lends his name to the annual "Dennis Quaid Charity Weekend" (formerly the "Jiffy Lube/Dennis Quaid Charity Classic") in Austin, Texas. The golf tournament attracts numerous celebrities with the proceeds split among local children's charities. He is a member of the Bel-Air Country Club in Bel-Air and tries to stay at homes on private courses when he is on the road.

Quaid works with the charity "International Hospital for Children in New Orleans." He makes trips to Central America to help build medical clinics and transport sick children back to the United States for treatment they cannot get locally.

• Crazy Mama (1975)
• I Never Promised You a Rose Garden (1977)
• September 30, 1955 (1977)
• Are You in the House Alone? (1978)
• Our Winning Season (1978)
• The Seniors (1978)
• Breaking Away (1979)
• The Long Riders (1980)
• Gorp (1980)
• All Night Long (1981)
• Caveman (1981)
• The Night the Lights Went Out in Georgia (1981)
• Stripes (1981)
• Tough Enough (1983)
• Jaws 3-D (1983)
• The Right Stuff (1983)
• Dreamscape (1984)
• Enemy Mine (1985)
• The Big Easy (1987)
• Innerspace (1987)
• Supsect (1987)
• D.O.A. (1988)
• Everybody's All-American (1988)
• Great Balls of Fire! (1989)
• Come See the Paradise (1990)
• Postcards from the Edge (1990)
• Wilder Napalm (1993)
• Undercover Blues (1993)
• Flesh and Bone (1993)
• A Century of Cinema (1994)
• Wyatt Earp (1994)
• Something to Talk About (1995)
• Dragonheart (1996)
• Gang Related (1997)
• Switchback (1997)
• Savior (1998)
• The Parent Trap (1998)
• Playing by Heart (1998)
• Any Given Sunday (1999)
• Frequency (2000)
• Traffic (2000)
• Dinner With Friends (2000)
• The Rookie (2002)
• Far from Heaven (2002)
• Cold Creek Manor (2003)
• The Alamo (2004)
• The Day After Tomorrow (2004)
• In Good Company (2004)
• Flight of the Phoenix (2004)
• Yours, Mine and Ours (2005)
• American Dreamz (2006)
• Vantage Point (2007)
• The Horsemen (2007)