Sanctuary is the story of Horace Benbow, a lawyer who returns to his ancestral home in Mississippi after becoming fed up with married life. Benbow becomes embroiled in his capacity as an attorney in the crimes of a gang of bootleggers led by Goodwin, a short-tempered alcoholic who is wrongly accused of the murder of his associate, the simple-minded Tommy. Goodwin is hanged after a farcical trial. The guilty party, a vicious sociopath named Popeye, escapes only to be later hanged for an unrelated crime. Benbow returns home, defeated.