Walter Winchell received a reported $25,000 per episode for his narration on this series. With his signature machine gun dialogue delivery, he could apparently rack up almost 200 words per minute.

According to testimony from Aladena Fratianno, (Jimmy the Weasel), a Mafia boss-turned-FBI informant, the Chicago family of the Mafia ordered the assassination of producer Desi Arnaz, because they didn't like (a) the fact that the success of the show was focusing attention on the Mafia and (b) the show's portrayal of Italians. Fratianno said that two hitmen hid themselves near Arnaz's house one night waiting for him to show up, but he never did. Shortly afterwards, the assassination order was rescinded when it was realized that Arnaz's murder would cause the Mafia more trouble than it was worth.

Robert Stack (Eliot Ness) and Walter Winchell (Narrator) are the only actors to appear in all 119 episodes of the series.

Van Heflin and Van Johnson turned down the role of Eliot Ness. Fred MacMurray, Jack Lord, and Cliff Robertson were also considered for the part.

To counter some of the claims that the show was anti-Italian, later episodes gave a more prominent role to Agent Enrico Rossi (the Italian-American member of Ness' team) in order to show an Italian-American as a hero working for law and order. Rossi was played by Nicholas Georgiade, who was Greek.

This show was under constant attack by various groups that claimed it defamed the image of Italians and Italian-Americans.

Although Agent Jack Rossman (Steve London), the fifth member of The Untouchables, appeared in sixty-four episodes, he often had little or no lines of dialogue.

Nicholas Georgiade, who plays The Untouchable team member Enrico Rossi, had a small, uncredited role as a thug in Westinghouse Desilu Playhouse: The Untouchables: Part 1 (1959), the series pilot. In the movie, after The Untouchables raid a plant and round up the criminals, Georgiade plays the thug identified as "Frank Cotter, a gunman from New York" who quips to Ness that he'll read about Ness' obituary in jail, thus getting punched by Ness.

Agent Youngfellow was supposed to be a full-blooded Cherokee from Oklahoma. In this series, he is played by a Latino actor, Abel Fernandez.

In the series, Eliot Ness was portrayed as an FBI. Special Agent, but, in reality, was a Treasury Department Agent.

This series was (very loosely) based on the book Ness co-wrote with journalist Oscar Fraley (who, in turn, confessedly "embellished" Ness' role into the fall of Capone). In spite of Fraley's additions, in the book, Ness and his eleven agents are not reported as doing much more than busting alcohol shipments and depots, yet the series had Ness intervening in dozens of totally fictional events. As a witness of the time put it about the series, "not even two percent of it is true".

One of the groups that tried to end this show was the estate of Al Capone. It was their claim that this show was unfairly profiting from the Capone name.

In the early 1950s, "Desilu Productions" was prohibited from using the word "pregnant" on network television. At the end of the decade, when this series was produced, although euphemisms were often used, the word "prostitution" was used numerous times in the series.

Among the concessions made to Italian-American groups, the network and producers were allowed to use Italians and Italian names for criminals based upon real people, but agreed that fictional criminal characters would be non-Italians.

The only actors to reprise their roles as members of The Untouchables from the series pilot, Westinghouse Desilu Playhouse: The Untouchables: Part 1 (1959) and Westinghouse Desilu Playhouse: The Untouchables: Part 2 (1959), are Robert Stack as Eliot Ness and Abel Fernández as William Youngfellow. All of the other team members were re-cast for the series.

With his visage and size (almost 6 foot), Bruce Gordon made a memorable Frank Nitti. In reality, the real Frank "The Enforcer" Nitti stood just under 5' 5."

In this series, Frank Nitti is shown as becoming the acting head of the Capone organization after Al Capone was sent to prison. It is believed that Frank Nitti was only a figurehead while the real person in power, very much unlike Capone, worked to keep out of the public eye.

Desi Arnaz and his Desilu Productions had a long standing relationship with CBS. When the pilot was a huge success, a series was offered to the network. Reportedly, it was turned down by the highly respected vice president of the network, Hubbell Robinson, and the network chairman, William S. Paley, agreed. Arnaz offered it to rival network ABC who picked it up resulting in a huge hit for that network.

An unusual feature of this series is that the episodes are not sequential. Each episode can shift forwards or backwards in time by years. This is obvious by seeing Frank Nitti killed in season one, yet still appearing in later seasons.