Woodrell was born in Springfield, Missouri, (for birth date and location) in the southwestern corner of the state. He grew up in northern Missouri and dropped out of high school to join the Marines. Later he earned a BA from the University of Kansas and a MFA from the Iowa Writers' Workshop.

He lives in West Plains, Missouri in the Ozarks, and is married to the novelist Katie Estill.

Woodrell has set most of his eight novels in the Missouri Ozarks, a landscape which he knew from childhood. He has created novels based on crime, a style he termed "country noir", a phrase which has been adopted by commentators on his work.

In addition to finding readers for his fiction, Woodrell has had two novels adapted for films.Woodrell's second novel, Woe to Live On (1987), was adapted for the 1999 film Ride with the Devil, directed by Ang Lee.

The more recent Winter's Bone (2006) was adapted by writer and director Debra Granik for a film of the same title, released commercially in June 2010 after winning two awards at the Sundance Film Festival, including the Grand Jury Prize for a dramatic film. Several critics have called it one of the best films of the year and an American classic.