Carlo Gambino was born on August 24, 1900, in Palermo, Italy where he was exposed to mafia activity. The Honored Society, what became known as the Mafia, developed in Palermo and western Sicily. This criminal brotherhood arose out of the lower class as a reaction to centuries of foreign tyranny. Gambino grew up in a part of Palermo that was completely overrun by the Mafia.

Through relatives of his mother, whose maiden name was Castellano, Gambino joined the Mafia. He arrived in the United States as an illegal alien in 1921. During World War II, Gambino profited in the black market of U.S. stamps issued for purchasing governmentally controlled goods. The government rationed gasoline, groceries, and luxury items. Citizens were given a limited number of wartime stamps to purchase these goods. Gambino and his associates trafficked in these wartime stamps. Teams of safecrackers would steal rationed stamps from government vaults or pay corrupt officials for the stamps and then deal in these stamps on the black market.

In 1957, Gambino arranged the murder of his boss, Albert Anastasia, and became boss of the largest and most influential organized crime family in the United States. Gambino died of natural causes in his Long Island home in 1975. His cousin and brother-in-law, Paul Castellano, became boss of the family in 1977. In 1985, John Gotti arranged for Castellano to be killed much the same way Gambino did Anastasia. Gotti succeeded Castellano as the Gambino crime family boss.