During the early 1960s, Salemme participated in the Irish Gang Wars in Boston. Testifying before Congress in 2003, Salemme admitted to murdering numerous rival gang members in Charlestown, Massachusetts:

"The Hugheses, the McLaughlins, they were all eliminated, and I was a participant in just about all of them, planned them and did them."
In 1968, Salemme arranged a car bombing of John Fitzgerald, a lawyer representing Patriarca mob informant Joseph Barboza. The point of the attack was to scare Barboza into not testifying against Raymond Patriarca and other mob leaders. Fitzgerald survived the attack, but lost his left leg. It was later established in testimony by several witnesses and confirmed by the U.S. House of Representatives Organized Crime unit investigation that Salemme was involved in the bombing, but did not carry it out.

After the unsuccessful attack, Salemme went into hiding. He remained a fugitive until 1972, when he was captured by FBI agent John Connolly.