The pilot for the series, a two-part episode entitled "The Untouchables", originally aired on CBS's Westinghouse Desilu Playhouse on April 20 and 27, 1959.

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.

As the series continued, a highly fictionalized portrayal of Ness and his crew developed as all-purpose, multiagency crime fighters who went up against an array of 1930s-era gangsters and villains, 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 ominous theme music by Nelson Riddle and its shadowy black-and-white photography, which was influenced by film noir.

The show drew harsh criticism from some Italian Americans, including Frank Sinatra,[6] who felt it promoted negative stereotypes of them as mobsters and gangsters.

In the first episode of the first season, the character of "Agent (Rico) Rossi", a person of Italian extraction who had witnessed a gangland murder, was added to Ness's team.

In protest formation outside the ABC New York headquarters, they had come together to urge the public boycott of Liggett & Myers Tobacco Company (L&M) products, including Chesterfield cigarettes, the lead sponsor of The Untouchables.

Four days after the picket of ABC, L&M, denying it had bowed to intimidation, announced it would drop its sponsorship of The Untouchables, maintaining the decision was based on network scheduling conflicts.

The following week, the head of Desilu, Desi Arnaz (who had attended high school with Capone's son Albert), in concert with ABC and the "Italian-American League to Combat Defamation", issued a formal three-point manifesto: The series also incurred the displeasure of the powerful director of the Federal Bureau of Investigation, J. Edgar Hoover, when the fictionalized scripts depicted Ness and his Treasury agents involved in operations that were actually the province of the FBI.

The producers agreed to insert a spoken disclaimer on future broadcasts of the episode stating that the FBI had primary responsibility for the Barker case.

** The character of Untouchable William Youngfellow, portrayed by Abel Fernandez, has been mistakenly referred to by Saturday Night Live actor Dan Aykroyd as "Youngblood".

Arnaz had had a long business relationship with CBS, which had aired many Desilu programs, including I Love Lucy and The Lucy–Desi Comedy Hour.

Some segments were released to theaters as movies: The Scarface Mob (from the two-part pilot), The Alcatraz Express (from "The Big Train"), and The Gun of Zangara (from "Unhired Assassin").

It also inspired films such as Al Capone starring Rod Steiger, The Untouchables (with Kevin Costner), Gangster Squad, Mulholland Falls, and others.

[18][19] The Lebanon (Pa.) Daily News said of The Untouchables: "Between the hard-nosed approach, sharp dialogue, and a commendably crisp pace (something rare in dramatic TV at the time), this series is one of the few that remains fresh and vibrant.

[22] In Billy Wilder's Academy Award-winning 1960 movie The Apartment, a corporate telephone operator being romanced by an executive objects to the rescheduling of a tryst as it will conflict with the broadcasting of The Untouchables.