On the morning of July 16, 1996, owner Bertha Tardy and three of her employees were murdered execution-style inside her furniture store in the quiet town of Winona, Mississippi. All four died of gunshot wounds to the head. Twenty-six-year-old Curtis Flowers became a suspect almost immediately when investigators learned that he'd been fired from the store days earlier. No murder weapon was ever found, but a gunshot residue test conducted on that day revealed one particle on Curtis' right hand. Flowers was arrested and went on to become one of the most tried defendants in history with the same District Attorney presiding for 21 years over a total of six trials and overturned verdicts. Now he faces a possible 7th trial while he continues to maintain his innocence.

Investigators Charlie Saums, Ira Todd and Joe Kennedy are on the ground in Winona, Mississippi, re-investigating the Curtis Flowers case. Flowers is convicted of a quadruple homicide for which he maintains his innocence. The investigators turn the spotlight on the state's investigation, as they start to realize that the police and prosecution may not have been as thorough as they should have. District Attorney Doug Evans has prosecuted Curtis in all six trials. In spite of repeated attempts to reach Evans, he refuses to be interviewed, pending a state Supreme Court decision, and a possible seventh trial. The investigators take to the streets, trying to learn what they can about how the prosecution was conducted.

Angie Dodge was found brutally murdered in her Idaho Falls apartment, stabbed multiple times, sexually assaulted and ejaculated upon postmortem. After six months without leads, the police thought they got a break when a friend of Angie's was arrested for rape at knifepoint. They questioned his friends, including Christopher Tapp, who they grilled for 28 hours. The grueling interrogation and leading questions led Tapp to confess to the crime. He was tried, found guilty, and sentenced to 30 years to life in prison. Tapp claims he's innocent. Videotapes of Tapp's confession show his story varying wildly from interrogation to interrogation, until finally he confesses. The Wrong Man team engages former LA County homicide detective, Danny Smith, to take a crack at the case. Even the victim's mother no longer believes Tapp murdered her daughter. Her own search produced new leads and persons of interest that Danny examines while conducting his own investigation to try and find the real killer.