After a classical education at the Portsmouth Abbey School, Buckley graduated from Jonathan Edwards College, Yale University in 1975, as a member of Skull and Bones. He became managing editor of Esquire Magazine.

In 1981, he moved to Washington, DC, to work as chief speechwriter for Vice President George H. W. Bush. This experience led to his novel The White House Mess, a satire on White House office politics and political memoirs. (The title refers to the White House lunchroom, which is known as the "mess" because the Navy operates it.)

Thank You for Smoking is another satire, its protagonist a lobbyist for the tobacco industry, Nick Naylor. He followed that with more humor about Washington in the form of Little Green Men, about the government agency investigating UFO sightings. His No Way To Treat A First Lady has the president's wife on trial for assassinating her husband and Florence of Arabia is about a do-gooding State Department bureaucrat in the Middle East. His one serious novel, Wet Work, is about a billionaire businessman avenging his granddaughter's death from drugs.

Thank You for Smoking was adapted into a movie written and directed by Jason Reitman, and starring Aaron Eckhart. It was released on 17 March 2006.

Buckley also wrote the non-fiction Steaming To Bamboola, about the merchant marine, as well as contributed to an oral history of Milford, Connecticut, and is an editor at Forbes Magazine. Buckley has written for most national newspapers and magazines, including The New York Times, The Wall Street Journal, The Washington Post, Time, The Atlantic Monthly, Smithsonian, US News & World Report, Vanity Fair, Vogue, Conde Nast Traveler and numerous humorous essays in The New Yorker.

For a brief time in summer and fall 2008, Christopher Buckley also wrote the back-page column for National Review, the conservative magazine founded by his father. This came to an end after Buckley endorsed the 2008 Democratic Presidential Nominee Barack Obama in October 2008. Buckley's endorsement, entitled "Sorry Dad, I'm Voting for Obama", appeared in The Daily Beast. He chose The Daily Beast to avoid complications with National Review. After many readers and contributors expressed their displeasure, Buckley resigned from National Review. Buckley continues to write columns for The Daily Beast.

He is married to Lucy Gregg Buckley with whom he has two children, Caitlin and William (born in 1988 and 1991). He also has a son Jonathan (born 2000), from a relationship with former Random House publicist Irina Woelfle.

Satirical novels

• The White House Mess (1986)
• Thank You for Smoking (1994)
• God Is My Broker : A Monk-Tycoon Reveals the 7½ Laws of Spiritual and Financial Growth (1998) (written with John Tierney)
• Little Green Men (1999)
• No Way to Treat a First Lady (2002)
• Florence of Arabia (2004)
• Boomsday (2007)
• Supreme Courtship (2008)

Films based on Buckley's novels

• Thank You for Smoking (2006) (Directed by Jason Reitman, Screenplay also by Reitman)
• Little Green Men (In pre-production; scheduled to be released in 2011) (Directed by Whit Stillman, Screenplay by Sean Bates and Gregory Mackenzie)

Travelogues

• Steaming to Bamboola - The World of a Tramp Freighter (1983)
• Washington Schlepped Here: Walking in the Nation's Capital (2003)

Other

• My Harvard, My Yale (1981) (contributor, segment "Stoned in New Haven") (university biography)
• Campion: A Play in Two Acts (1990) (written with James Macguire) (play)
• Wet Work (1991) (novel)
• Wry Martinis (1997) (collected humor and journalism)
• A Memoir (2009) ISBN 0-44-654094-3 (Biographical)