The series originally focused on the efforts of a real-life squad of Prohibition agents employed by the United States Department of the Treasury and led by Eliot Ness (Stack), that helped bring down the bootleg empire of "Scarface" Al Capone, as described in Ness's bestselling 1957 memoir. This squad was nicknamed "The Untouchables", because of their courage and honesty; they could not be bribed or intimidated by the Mob. Eliot Ness himself had died suddenly in May 1957, shortly before his memoir and the subsequent TV adaptation were to bring him fame beyond any he experienced in his lifetime.
The pilot for the series was a two-part episode entitled "The Untouchables" originally aired on CBS's Westinghouse Desilu Playhouse on April 20 and 27, 1959. Later retitled "The Scarface Mob", these episodes, which featured Neville Brand as Al Capone, were the only episodes in the series to be more-or-less directly based on Ness's memoir, and ended with the conviction and imprisonment of Capone. CBS, which had broadcast most of Desilu's television output since 1951 beginning with I Love Lucy, was offered the new series following the success of the pilot film. Chairman William S. Paley rejected it on the advice of network vice president Hubbell Robinson. ABC agreed to air the series, and The Untouchables premiered on October 15, 1959. In the pilot movie, the mobsters generally spoke with unrealistic pseudo-Italian accents, but this idiosyncratic pronunciation was dropped when the series debuted.
The weekly series first followed the premise of a power struggle to establish a new boss in Capone's absence (for the purpose of the TV series, the new boss was Frank Nitti, although this was contrary to fact). As the series continued, there developed a highly fictionalized portrayal of Ness and his crew as all-purpose crime fighters who went up against an array of gangsters and villains of the 1930s, including Ma Barker, Dutch Schultz, Bugs Moran, Vincent "Mad Dog" Coll, Legs Diamond, Lucky Luciano, and in one episode, Nazi agents.
The terse narration by gossip columnist Walter Winchell, in his distinctive New York accent, was a stylistic hallmark of the series, along with its melancholy theme music by Nelson Riddle and its shadowy black-and-white photography, influenced by film noir.