In 1994 in West Memphis, Arkansas, three teenage boys—Damien Echols, Jessie Misskelley, Jr. and Jason Baldwin—were tried and convicted for the brutal murder of three eight-year-old boys. The murders were portrayed throughout the trials as being motivated by a satanic cult and the teens were painted as being vicious, soul-less individuals. All three were found guilty and sentenced to spend virtually a lifetime in prison; Damien was sentenced to death. But many believed there was more to the story than just a satanic murder. Many believed the teens were innocent.

Since the 1996 release of the documentary Paradise Lost: The Child Murders at Robin Hood Hills and its subsequent sequels, which painted a very different picture of the murders and the trials, thousands have openly shown support for the innocence of Damien, Jessie and Jason, dubbed the West Memphis Three. Even celebrities like Johnny Depp and Eddie Vedder have spoken out in the name of justice.

West of Memphis follows the lives of the three teenage boys, who spent 18 years in prison before getting the chance to clear their names. The film explores the failure of the justice system in Arkansas by shedding some light on a case that still haunts the American South.