It drew its title, inspiration and original format from the CBS News documentary 48 Hours on Crack Street, which aired in September 1986, centering on the drug crisis plaguing a number of U.S. neighborhoods.

One of the contributors to that program, CBS News correspondent Harold Dow, had been a member of the 48 Hours on-air staff since its premiere.

Dan Rather, at the time also serving as anchor of the CBS Evening News, was the primary host of 48 Hours for its first 14 years on the air.

These recordings were later used in 2011 as evidence in court to convict Arias, the first time the program's interviews had ever been used in a death penalty trial.

The program was revamped in 2002, when Lesley Stahl took over hosting duties from Dan Rather, and its title was changed to 48 Hours Investigates.

The title was changed again to 48 Hours Mystery in 2004, and with its single-topic format, it does not use a single host but is narrated by the reporter assigned to the story.