Rio's involvement in crime began early in life, and included robbery, burglary, and auto theft.

On January 17, 1921, Rio—along with Robert O'Neill and Thomas Dyer—robbed a mail train at Chicago's Union Station, stealing bonds worth $482,000.

[3] Rio's ability to escape punishment could not be attributed to good luck or innocence but rather to the bribing of judges and the intimidation and murder of witnesses.

In time, criminal elements dubbed him "Slippery" Frank Rio for his knack of evading trial.

[4] Rio's criminal exploits brought him to the attention of Al Capone, leader of the Chicago Outfit.

[5] Rio also is said to have foiled a plot by Albert Anselmi, John Scalise and Joseph Guinta to depose Capone and take over the Chicago Outfit.

Capone arranged to have himself jailed in Philadelphia after the conference in order to avoid the numerous "murder-for-hire" rackets that were hunting him.

Several gangsters also accused Rio of having "gone soft" due to his years of "high living" he had enjoyed alongside Capone.

In 1932, the Chicago Outfit sent Rio to New Jersey to offer the mob's assistance in helping Charles Lindbergh find his kidnapped baby son.

Police later said that gang members became involved in his burial because they wanted to divide up Rio's gang-owned assets before news of his death hit the streets.