After the murder of the judges Giovanni Falcone and Paolo Borsellino, Buscetta gave further testimony to the Antimafia Commission linking Italian politicians to the Mafia.

In 1949, he moved to Argentina and then to Brazil, where he opened a glassworks store, but in 1956, he returned to Palermo where he joined Angelo La Barbera and Salvatore "Ciaschiteddu" Greco together with mafiosi Antonino Sorci, Pietro Davì and Gaetano Badalamenti, dealing with the cigarette and drug smuggling.

[11] Buscetta moved to Brazil, having undergone plastic surgery and vocal cord surgery,[1] he set up a drug trafficking network, but on 3 November 1972, was arrested by the Brazilian military government, and subsequently extradited to Italy exactly one month later where he began a ten-year sentence at Palermo's Ucciardone prison for drug trafficking, reduced to eight years after appeal.

[1] In February 1980, he was granted "half-freedom", immediately fleeing back to Brazil to escape the brewing Second Mafia War instigated by Salvatore Riina.

[13] This was followed by the deaths of his brother Vincenzo, son-in-law Giuseppe Genova, brother-in-law Pietro and four of his nephews, Domenico and Benedetto Buscetta, and Orazio and Antonio D'Amico.

[20] Buscetta revealed information to Falcone for 45 days,[3] explaining the inner workings and hierarchical structures of Cosa Nostra including the Sicilian Mafia Commission,[21] that, until then, were unclear because of the strict code of silence.

[23] Buscetta refused to speak with Falcone of the political ties of Cosa Nostra because, in his opinion, the state was not ready for statements of that magnitude, and proved to be quite general on that subject.

[25][26] He testified in the Pizza Connection Trial, which took place in 1985 in New York and saw defendants Gaetano Badalamenti and other Sicilian-American mafiosi accused of drug trafficking.

[28] Buscetta helped judges Falcone and Paolo Borsellino achieve significant success in the fight against organized crime, which led to 475 Mafia members indicted and 338 convicted; those sentences were upheld in 1992.

[22][29] In mid-1992, following the bomb attacks in which Falcone and Borsellino were killed, Buscetta began to speak of the political ties of the Cosa Nostra with magistrates, accusing Salvo Lima, killed a few months earlier, and Giulio Andreotti of being the main political referents of the organization; in particular, he reported that he had known Lima personally since the late 1950s, and had met him last in 1980, and also reported that he had learned that the murder of the journalist Mino Pecorelli in 1979 would have been carried out in Andreotti's interest.

"[35] Buscetta died of cancer on 2 April 2000, aged 71, having lived out most of his life in hiding with his third wife and family in Florida, United States, under false names.

Also released in 2019, Our Godfather is a documentary by Mark Franchetti and Andrew Meier which includes onscreen testimony by Buscetta's third wife and surviving children "who still live in anonymity because of fear of reprisal", according to one review.