Samuel Little, originally named Samuel McDowell, was born on June 7, 1940, in Reynolds, Georgia. The son of Bessie Mae Little, who Samuel claimed was a teenage prostitute and may have been incarcerated at the time of his birth, had a turbulent start to life. Census records from that period list his mother as a maid and identify his father as 19-year-old Paul McDowell. Shortly after his birth, his family relocated to Lorain, Ohio, where he was raised primarily by his grandmother.

Little's school years at Hawthorne Junior High School were marked by disciplinary problems and poor academic performance.

From an early age, he harbored dark sexual fantasies about strangling women, which were initially sparked when he was just a kindergartener. This fascination grew during his teenage years as he collected true crime magazines that often featured stories of women being choked.

His criminal activities began in earnest in 1956 when he was convicted of breaking and entering in Omaha, Nebraska, and placed in a juvenile institution. At the time, his mother's location was noted as "whereabouts unknown." In the late 1960s, Little moved to Florida to be with his mother and worked various jobs, including as a cemetery worker and an ambulance attendant. His life took a nomadic turn as he traveled widely and encountered the law frequently, getting arrested in eight states for a range of offenses from driving under the influence to armed robbery and rape.

Little also claimed to have taken up boxing while in prison, often referring to himself as a former prizefighter.

In 1982, Little faced murder charges for the first time in Pascagoula, Mississippi, for the death of 22-year-old Melinda Rose LáPree. Although he was not indicted due to insufficient evidence, he was soon tried in Florida for the murder of Patricia Ann Mount, whose body was discovered in 1982. Despite witness testimonies placing him with Mount shortly before her disappearance, Little was acquitted in 1984 due to doubts about the credibility of the testimonies.

Post-acquittal, Little moved to California, where his criminal activities escalated. He was arrested in 1984 for the kidnapping, beating, and strangling of 22-year-old Laurie Barros, who survived. A subsequent arrest occurred when he was found with another beaten and strangled woman in his car. He served two and a half years for both crimes, released in 1987, only to continue his murderous spree, claiming at least ten more victims.

Little’s past caught up with him in 2012 when he was arrested at a homeless shelter in Kentucky and extradited to California to face charges based on DNA evidence linking him to three murders between 1987 and 1989. The subsequent investigations uncovered his involvement in dozens more unsolved murders from the 1980s, leading to new charges.

Tried in 2014, Little was convicted for the murders of three women based on DNA evidence and witness testimony about his long history of violence. He was sentenced to life without parole, maintaining his innocence until the end despite his numerous confessions to other murders, which were detailed and prolific, claiming lives across many states from the 1970s through to 2005.

In a chilling end to his life story, Little confessed to over 90 murders, making him one of the most prolific serial killers in American history. His confessions included previously cold cases, with many of his admissions verified by law enforcement, yet many of his victims remain unidentified. Little passed away on December 30, 2020, in a Los Angeles County hospital.