His first novel, Cold Mountain (Atlantic Monthly Press, 1997.ISBN 0-87113-679-1), traces the journey of Inman, a wounded deserter from theConfederate army near the end of the American Civil War.The work is rich in the culture and sensibilities of the North Carolina mountains and is based on local history and stories handed down by Frazier's father about Frazier's great-great-uncle William Pinkney Inman. Inman, who was from the area around Cold Mountain in western North Carolina, served in the Confederate Army from which he deserted after being wounded twice and is reputedly buried in a local cemetery. The real Inman served as a private in Company F of the 25th North Carolina Infantry, and his regiment did participate in the fighting in the Siege of Petersburg, including the Battle of the Crater.

The novel won the 1997 National Book Award and was adapted as a film of the same title by Anthony Minghella in 2003.

Frazier's second novel Thirteen Moons was published in October 2006 by Random House, and traces the story of one man across a century of change in America. Also set in western North Carolina, the novel traces one white man's involvement with the Cherokee Indians just before, during and after their removal to Oklahoma. It is a story of struggle and triumph against the emerging U.S. government's plan to remove native Cherokee people to Oklahoma. Based on the success of Cold Mountain, Frazier was offered an $8 million advance for Thirteen Moons.

Frazier has said that his next book will be different, in that it takes place in the 20th century. However, the setting will still be the Appalachian Mountains.