McCarthy's first novel, The Orchard Keeper, was published by Random House in 1965. He decided to send the manuscript to Random House because "it was the only publisher [he] had heard of." At Random House, the manuscript found its way to Albert Erskine, who was William Faulkner's editor until Faulkner's death in 1962. Erskine continued to edit McCarthy for the next twenty years.

In the summer of 1965, using a Traveling Fellowship award from The American Academy of Arts and Letters, McCarthy shipped out aboard the liner Sylvania, hoping to visit Ireland. While on the ship, he met Anne DeLisle, who was working on the ship as a singer. In 1966, they were married in England. Also in 1966, McCarthy received a Rockefeller Foundation Grant, which he used to travel around Southern Europe before landing in Ibiza, where he wrote his second novel, Outer Dark. Afterward he returned to America with his wife, and Outer Dark was published in 1968 to generally favorable reviews.

In 1969, McCarthy and his wife moved to Louisville, Tennessee, and purchased a barn, which McCarthy renovated, even doing the stonework himself. Here he wrote his next book, Child of God, based on actual events. Child of God was published in 1973. Like Outer Dark before it, Child of God was set in southern Appalachia. In 1976, McCarthy separated from Anne DeLisle and moved to El Paso, Texas. In 1979, his novel Suttree, which he had been writing on and off for twenty years, was finally published.

Supporting himself with the money from his 1981 MacArthur Fellowship, he wrote his next novel, Blood Meridian, or the Evening Redness in the West, which was published in 1985. The book has grown appreciably in stature in literary circles. In a 2006 poll of authors and publishers conducted by The New York Times Magazine to list the greatest American novels of the previous quarter-century, Blood Meridian placed third, behind only Toni Morrison's Beloved and Don DeLillo's Underworld.

McCarthy finally received widespread recognition in 1992 with the publication of All the Pretty Horses, which won the National Book Award and the National Book Critics Circle Award. It was followed by The Crossing and Cities of the Plain, completing the Border Trilogy. In the midst of this trilogy came The Stonemason, McCarthy's second dramatic work. He had previously written a film for PBS in the 1970s, The Gardener's Son. McCarthy's next book, 2005's No Country for Old Men, stayed with the western setting and themes, yet moved to a more contemporary period. It was adapted into a film of the same name by the Coen Brothers, winning four Academy Awards and more than 75 film awards globally. McCarthy's latest book, The Road, was published in 2006 and won international acclaim and the Pulitzer Prize for literature. A film adaptation directed by John Hillcoat, written by Joe Penhall, and starring Viggo Mortensen and Kodi Smit-McPhee was released on November 25, 2009. Also in 2006, McCarthy published a play entitled The Sunset Limited.

McCarthy is at work on three new novels. One is set in 1980s New Orleans and follows a young man as he deals with the suicide of his sister. According to McCarthy, this will be his first work to feature a prominent female character. He also states that the new novel is "long". The Texas State University-San Marcos recently acquired McCarthy's papers.

McCarthy now lives in the Tesuque, New Mexico, area, north of Santa Fe, with his wife, Jennifer Winkley, and their son, John. He guards his privacy. In one of his few interviews (with The New York Times), McCarthy reveals that he is not a fan of authors who do not "deal with issues of life and death," citing Henry James and Marcel Proust as examples. "I don't understand them," he said. "To me, that's not literature. A lot of writers who are considered good I consider strange." McCarthy remains active in the academic community of Santa Fe and spends much of his time at the Santa Fe Institute, which was founded by his friend, physicist Murray Gell-Mann.

Talk show host Oprah Winfrey chose McCarthy's 2006 novel The Road as the April 2007 selection for her Book Club. As a result, McCarthy agreed to his first television interview, which aired on The Oprah Winfrey Show on June 5, 2007. The interview took place in the library of the Santa Fe Institute; McCarthy told Winfrey that he does not know any writers, and much prefers the company of scientists. During the interview he related several stories illustrating the degree of outright poverty he has endured at times during his career as a writer. He also spoke about the experience of fathering a child at an advanced age, and how his now-eight-year-old son was the inspiration for The Road. McCarthy noted to Oprah that he prefers "simple declarative sentences" and that he uses capital letters, periods, an occasional comma, a colon for setting off a list, but "never a semicolon." He does not use quotation marks for dialogue and believes there is no reason to "blot the page up with weird little marks."

According to Wired magazine, McCarthy's Olivetti Lettera 32 typewriter was put up for auction at Christie's. The Olivetti Lettera 32 has been in his care for 46 years, since 1963. He picked up the used machine for $50 from a pawn shop in Knoxville, Tennessee. McCarthy reckons he has typed around five million words on the machine, and maintenance consisted of “blowing out the dust with a service station hose”. The typewriter was auctioned on Friday, December 4, 2009 and the auction house, Christie’s, estimated it would fetch between $15,000 and $20,000; it sold for $254,500. The Olivetti’s replacement for McCarthy to use is another Olivetti, bought by McCarthy’s friend John Miller for $11. The proceeds of the auction are to be donated to the Santa Fe Institute, a nonprofit interdisciplinary scientific research organization.

Family

Children:

• Cullen McCarthy, son (with Lee Holleman)
• John Francis McCarthy, son (with Jennifer Winkley)

Marriages:

• Lee McCarthy, née Holleman, (1961) divorced
• Annie DeLisle, (1967 - divorced 1981)
• Jennifer Winkley (married as of 2007)

Novels

• The Orchard Keeper (1965) ISBN 0-679-72872-4
• Outer Dark (1968) ISBN 0-679-72873-2
• Child of God (1974) ISBN 0-679-72874-0
• Suttree (1979) ISBN 0-679-73632-8
• Blood Meridian, Or the Evening Redness in the West (1985) ISBN 0-679-72875-9
• All the Pretty Horses (1992) ISBN 0-679-74439-8
• The Crossing (1994) ISBN 0-679-76084-9
• Cities of the Plain (1998) ISBN 0-679-74719-2
• No Country for Old Men (2005) ISBN 0-375-70667-4
• The Road (2006) ISBN 0-307-38789-5
• The Passenger (working title, TBA)

Screenplays

• The Gardener's Son (1976) ISBN 0-880-01481-4

Plays

• The Stonemason (1995) ISBN 978-0679762805
• The Sunset Limited (2006) ISBN 0-307-27836-0

The comprehensive archive of Cormac McCarthy's personal papers is preserved at the Wittliff collections, Texas State University, San Marcos, Texas. The McCarthy papers consists of 98 boxes (46 linear feet). The acquisition of the Cormac McCarthy Papers resulted from years of ongoing conversations between McCarthy and Southwestern Writers Collection founder, Bill Wittliff, who negotiated the proceedings. The Southwestern Writers Collection / Wittliff collections also holds The Wolmer Collection of Cormac McCarthy, which consists of letters between McCarthy and bibliographer J. Howard Woolmer, and four other related collections.