Charles Portis was born in El Dorado, Arkansas to Samuel Palmer and Alice Waddell Portis on December 28, 1933. He was raised and educated in various towns in southern Arkansas. The family, which included two brothers and one sister, settled in Hamburg. Portis served in the U.S. Marine Corps during the Korean War, reaching the rank of sergeant. He received his discharge in 1955. He enrolled in the University of Arkansas at Fayetteville and graduated with a degree in journalism in 1958.

He began his career in journalism while in school, writing for both the University of Arkansas at Fayetteville student newspaper, Arkansas Traveler, and the Northwest Arkansas Times. After he graduated, he worked for various newspapers as a reporter, including almost two years at the Arkansas Gazette, for which he wrote the "Our Town" column. He worked for four years at the New York Herald-Tribune. His work for the New York Herald Tribune allowed him to return to the South on many occasions to cover civil rights—related stories. After serving a year as a reporter and the London bureau chief of the New York Herald Tribune, he left journalism in 1964, returned to Arkansas, and began writing fiction full-time.

His first novel, Norwood (1966), established his preference for travel narratives with deadpan dialogue combined with amusing observations on American culture. Based in the mid-1950s, the novel’s plot revolves around Norwood Pratt, a young, naïve, goodhearted ex-Marine living in Ralph, Texas, who is persuaded by con-man Grady Fring (the first of several such characters inhabiting Portis’s novels) to transport a pair of automobiles to New York City. Norwood comes into contact with a variety of unusual people on the way to New York and back, including ex-circus midget Edmund Ratner ("the world’s smallest perfect fat man"), Joann ("the college educated chicken"), and Rita Lee, a girl Norwood woos and wins on the bus ride back to the South. Norwood was made into a movie in 1970, starring Glen Campbell playing the title character, with Kim Darby and Joe Namath.

Like Norwood, his novel True Grit (1968) was serialized in condensed form in the Saturday Evening Post. His most successful work, this novel is told by Yell County native Mattie Ross who, at the time of the events described in the novel, was a prim, shrewd, strong-willed, Bible-quoting 14 year-old girl. When her father is murdered in Fort Smith by a hired hand, Tom Chaney, she recruits Deputy Marshal Rooster Cogburn...in whom Mattie sees one possessed, like herself, of "grit"...to help her hunt down Chaney and his outlaw band to "avenge her father’s blood". Both satirical of Westerns and realistic, the novel succeeded through its taut story line, Mattie’s believable narrative voice, sharp dialogue, and a journalistic attention to details.

Both Norwood and True Grit became successful movies starring fellow Arkansan Glen Campbell. John Wayne won an Academy Award and a Golden Globe for Best Actor for his performance as Rooster Cogburn in True Grit, which was one of the top box office hits of 1969. True Grit was released on June 11, 1969, earning $14.25 million at the box office.

In the 1990s, Portis published short fiction and biographical pieces in The Atlantic Monthly, including "Combinations of Jacksons" and "I Don't Talk Service No More".

Portis is reclusive and travels frequently to Mexico.

Charles Portis has written five novels:

• 1966: Norwood
• 1968: True Grit
• 1979: The Dog of the South
• 1985: Masters of Atlantis
• 1991: Gringos