A graduate of the University of Chicago, Ness was 26 when, in 1929, he was hired as a special agent of the U.S. Department of Justice to head the Prohibition bureau in Chicago, with the express purpose of investigating and harassing Al Capone. Because the men, all in their 20s, whom he hired to help him were extremely dedicated and unbribable, they were nicknamed the Untouchables. The public learned of them when big raids on breweries, speakeasies, and other places of outlawry attracted newspaper headlines (reporters being invited to the raids). The Untouchables' infiltration of the underworld secured evidence that helped send Capone to prison for income-tax evasion.

Later, Ness was in charge of the alcohol-tax unit of the U.S. Department of the Treasury (1933–35) and then director of public safety in Cleveland, Ohio (1935–41). During World War II (1941–45), he was director of the Division of Social Protection of the Federal Security Agency in Washington, D.C. After the war he went into private business.