Galante was born on February 21, 1910 in New York. His parents, Vincenzo "James" Galante and Vincenza Russo, had emigrated to New York City in 1906 from Castellammare del Golfo, Sicily, where Vincenzo was a fisherman. Galante had two brothers, Samuel and Peter Galante, and two sisters, Josephine and Angelina Galante.
At the age of 10, Galante was sent to reform school due to his criminal activities. By the age of 15, he had dropped out of seventh grade.
At seventeen, Galante was serving time in Sing Sing for assault. Upon his release from prison, he returned to New York City and was soon head of a gang on the Lower East Side. As "button man" for Vito Genovese, he carried out assassinations. Most notorious was the 1943 murder of Carlo Tresca, publisher and editor of Il Martello (The Hammer), an anarchist weekly. Genovese, who fled from the United States to Italy in 1937 to escape murder charges, was involved in the Italian narcotics trade and was a flunky for Benito Mussolini (one of whose official programs was to eradicate the Mafia). The murder of Tresca was a favor for Mussolini. By 1952 Galante was a lieutenant in the Joe Bonanno crime family in New York City. Bonanno, like Galante's parents, was from Castellamare del Golfo. Bonanno's base of operations was a section of Williamsburg, Brooklyn, inhabited chiefly by immigrants from that village. His ambitions extended beyond the neighborhood: he was making inroads in Arizona, looking at Haiti and California, already running rackets in Canada. Galante (called Lillo or "The Cigar" in reference to his ever-present stogie), was Bonanno's main man in narcotics trafficking. He spoke several dialects of Italian and was fluent in Sicilian, Spanish, and French; thus he was the right man to travel abroad, arranging multimillion-dollar heroin deals. Having established the "French connection" from Italy through France and Montreal to New York, he became personal chauffeur to Bonanno, then an underboss. In 1960, Galante was indicted for drug violations. The case ended in a mistrial after the jury foreman broke his back in a fall. Indicted again in 1962 on a narcotics charge, Galante was convicted and sent to the federal penitentiary in Lewisburg, Pennsylvania. He served twelve years of a twenty-year sentence before release on parole. Meanwhile, Bonanno, having failed to become boss of bosses, in the bloody Banana War, had been forced by the other capos to retire to Tucson, Arizona, after he suffered a heart attack in 1968. Genovese died in prison in 1969. His mentors gone, Galante, while still in Lewisburg, told associates he was going to be the next head of organized crime. He was openly critical of Carlo Gambino, the most powerful underworld boss in New York City by the end of the 1960's, for discouraging trafficking in drugs, opposing expansion of membership in families, and taking a disloyal attitude toward traditions of the Mafia. Philip ("Rusty") Rastelli was head of the Bonanno family when Galante was paroled in 1974. He agreed to step down after his son-in-law was shot dead in a Brooklyn street. Galante next went after the drug trade Gambino had left untouched. In the next two years, more than twenty drug dealers in the Northeast were murdered, and the Bonanno family controlled almost all heroin passing through Canada to the United States. Its Canadian activities became so extensive that three lieutenants were settled in Canada under Steven Schwarz. Besides narcotics, the Bonanno family's illegal activities under Galante consisted of gambling, labor racketeering, loan-sharking, truck hijacking, extortion, and bankruptcy fraud. Its legal businesses included cheese companies, trucking, refuse carting, and garment and jewelry companies. It dictated policy and rates for the American gambling syndicate in Canada. In 1976, Gambino died a natural death. He had selected his brother-in-law Paul Castellano as his successor, but the real power in the family was Aniello ("Mr. Neil") Dellacroce. When Galante declared himself the next boss of bosses, a feud was inevitable. The Bonanno family had 200 soldiers; the Gambino family, 1, 000. More than twenty died before the ceasefire of 1978, when Galante went to jail for violating parole by associating with known criminals. The federal government placed Galante in solitary confinement in the penitentiary at Danbury, Connecticut, insisting they were protecting him because there was a contract on his life. Contending this assassination plot was a government invention, his lawyer, Roy Cohn, obtained his release. Galante immediately went to war, this time with the Genovese family, for control of drug operations in New York City. Mafia leaders had enough after eight Genovese soldiers were gunned down. At Boca Raton, Florida, Gerardo Catena, Santo Trafficante, Frank Tieri, Paul Castellano, Phil Rastelli (from prison), and Joe Bonanno (from retirement) agreed: Galante had to go. On the afternoon of July 12, 1979, Galante was driven to the Joe and Mary Italian American Restaurant, in the Bushwick section of Brooklyn, to have lunch with the owner, Joe Turano, who was Galante's cousin. Galante, Turano, Leonard Coppolla (an associate), and two others were sitting at a table on the patio at the back of the restaurant when three masked gunmen entered. One of them stepped within six feet and fired both barrels of a shotgun. Galante, hit in the eye and chest, was hurled on his back, dead, his cigar still sticking straight out from the middle of his mouth. Coppolla also died instantly. Turano died en route to a hospital. The other two escaped unharmed, and disappeared. The Bonanno family underboss at the time was Nicholas Marangella, who had run the organization during Galante's last stay in jail.
Galante stood around 5 feet 6 inches and weighed approximately 160 pounds.
Galante married Helen Marulli, by whom he had three children; James Galante, Camille Galante, and Angela Galante. For the last 20 years of his life, he actually lived with Ann Acquavella; the couple had two children together.
