In June 1975, Aiuppa allegedly participated in the Outfit decision to kill Giancana. The FBI suspected that the Outfit killed Giancana because he refused to share his offshore gambling profits from Mexico. Other Giancana allies, such as Johnny 'Johnny Handsome' Roselli, were also killed around the time of Giancana's death.

Santo Trafficante Jr. may have ordered the hit on Sam Giancana because he was afraid Giancana would testify about Mafia and CIA plots to kill Fidel Castro. If so, Trafficante probably got permission to kill Giancana from Chicago bosses Tony Accardo and Joseph Aiuppa. Johnny Roselli was definitely killed on Trafficante's orders when his body was found stuffed in an oil drum on the coast off Miami.

Some crime figures claimed that the CIA killed Giancana due to his role in the failed assassination plots against Cuban President Fidel Castro. However, there is no evidence to substantiate those claims.

In 1986, Aiuppa was convicted of skimming profits from Las Vegas casinos and received 28 years in prison.

Aiuppa approved Joseph Feriolla's decision to execute Tony "The Ant" Spilotro in March 1986. Spilotro had been Aiuppa's representative in Las Vegas and Aiuppa supposedly blamed him for his skimming arrest. That along with the fact that Spilotro was attracting too much law enforcement "heat" with all his other antics in Las Vegas put him in the hot seat with Outfit higher-ups. Spilotro and his brother Michael, a mob lackey and bit television actor, were found beaten and buried alive in a cornfield only four to five miles away from a large property owned by Aiuppa near Morocco, Indiana.

Aiuppa was released from prison on 1996. On February 22, 1997, Joseph Auippa died of natural causes at Elmhurst Hospital located in Elmhurst, Illinois