Salvatore Lucania was born on November 24, 1897, in Lercara Friddi, Sicily, Italy.

In April 1906, when Luciano was nine years old, the family emigrated to the United States. They settled in New York City in the borough of Manhattan on its Lower East Side, a popular destination for Italian immigrants.

At age 14, Luciano dropped out of school and started a job delivering hats, earning $7 per week. However, after winning $244 in a dice game, Luciano quit his job and began earning money on the street. That same year, Luciano's parents sent him to the Brooklyn Truant School.

By 1920, Luciano had met many future Mafia leaders, including Vito Genovese and Frank Costello, his longtime friend and future business partner through the Five Points Gang. That same year, Lower Manhattan gang boss Joe Masseria recruited Luciano as one of his gunmen. Around that same time, Luciano and his close associates started working for gambler Arnold "The Brain" Rothstein, who immediately saw the potential windfall from Prohibition and educated Luciano on running bootleg alcohol as a business.

On January 17, 1920, the Eighteenth Amendment to the U.S. Constitution took effect and Prohibition lasted until the amendment was repealed in 1933. The amendment prohibited the manufacture, sale, and transportation of alcoholic beverages. Demand for alcohol naturally continued, the resulting black market for alcoholic beverages providing criminals with an additional source of income.

By 1925, Luciano was grossing over $12 million a year. He had a net income of around $4 million each year after subtracting the costs of bribing politicians and police.

Luciano soon became a top aide in Masseria's criminal organization. In contrast to Rothstein, Masseria was uneducated, with poor manners and limited managerial skills. By the late 1920s, Masseria's main rival was boss Salvatore Maranzano, who had come from Sicily to run the Castellammarese clan. Maranzano refused to pay commissions to Masseria. Their rivalry eventually escalated into the bloody Castellammarese War and ultimately resulted in the deaths of both Maranzano and Masseria.

With Masseria gone, Maranzano reorganized the Italian-American gangs in New York City into Five Families headed by Luciano, Profaci, Gagliano, Vincent Mangano and himself. Maranzano promised that all the families would be equal and free to make money. However, at a meeting of crime bosses in Upstate New York, Maranzano declared himself capo di tutti capi ("boss of all bosses").

Luciano decided to eliminate Masseria (Lower Manhattan gang boss) . The war had been going poorly for Masseria, and Luciano saw an opportunity to switch allegiance. In a secret deal with Maranzano, Luciano agreed to engineer Masseria's death in return for receiving Masseria's rackets and becoming Maranzano's second-in-command. On April 15, Luciano invited Masseria and two other associates to lunch in a Coney Island restaurant. After finishing their meal, the mobsters decided to play cards. At that point, according to mob legend, Luciano went to the bathroom. Four gunmen then walked into the dining room and shot and killed Masseria.

By September 1931, Maranzano realized Luciano was a threat, and hired Vincent "Mad Dog" Coll, an Irish gangster, to kill him. However, Lucchese alerted Luciano that he was marked for death. On September 10, Maranzano ordered Luciano and Genovese to come to his office at the 230 Park Avenue in Manhattan. Convinced that Maranzano planned to murder them, Luciano decided to act first. He sent to Maranzano's office four Jewish gangsters whose faces were unknown to Maranzano's people. They had been secured with the aid of Lansky and Siegel. Disguised as government agents, two of the gangsters disarmed Maranzano's bodyguards. The other two, aided by Lucchese, who was there to point Maranzano out, stabbed the boss multiple times before shooting him. This assassination was the first of what would later be fabled as the "Night of the Sicilian Vespers."

The group's first test came in 1935, when it ordered Dutch Schultz to drop his plans to murder Special Prosecutor Thomas E. Dewey. Luciano argued that a Dewey assassination would precipitate a massive law enforcement crackdown; it has long been a hard and fast rule in the American underworld that police officers, federal agents and prosecutors are not to be harmed. A defiant Schultz told the Commission that he was going to kill Dewey (or his assistant David Asch) in the next three days. In response, the Commission quickly arranged Schultz's murder. On October 24, 1935, before he could kill Dewey or Asch, Schultz was murdered in a tavern in Newark, New Jersey.

On April 3, Luciano was arrested in Hot Springs on a criminal warrant from New York. The next day in New York, Dewey indicted Luciano and his accomplices on 60 counts of compulsory prostitution. Luciano's lawyers in Arkansas then began a fierce legal battle against extradition.

On April 6, someone offered a $50,000 bribe to Arkansas Attorney General Carl E. Bailey to facilitate Luciano's case. However, Bailey refused the bribe and immediately reported it.

On April 17, after all of Luciano's legal options had been exhausted, Arkansas authorities handed him to three NYPD detectives for transport by train back to New York for trial. When the train reached St. Louis, Missouri, the detectives and Luciano changed trains. During this switchover, they were guarded by 20 local policemen to prevent a mob rescue attempt.

The men arrived in New York on April 18, and Luciano was sent to jail without bail.

On May 13, 1936, Luciano's pandering trial began. Dewey prosecuted the case that Carter built against Luciano. He accused Luciano of being part of a massive prostitution ring known as "the Combination". During the trial, Dewey exposed Luciano for lying on the witness stand through direct quizzing and records of telephonecalls; Luciano also had no explanation for why his federal income tax records claimed he made only $22,000 a year, while he was obviously a wealthy man. Dewey ruthlessly pressed Luciano on his long arrest record and his relationships with well-known gangsters such as Masseria, Ciro Terranova, and Louis Buchalter.

On June 7, Luciano was convicted on 62 counts of compulsory prostitution.

On July 18, he was sentenced to 30 to 50 years in state prison, along with Betillo and others.

Luciano's legal appeals continued until October 10, 1938, when the U.S. Supreme Court refused to review his case. At this point, Luciano stepped down as family boss, and Costello formally replaced him.

On January 3, 1946, as a presumed reward for his alleged wartime cooperation (in WWII), Dewey reluctantly commuted Luciano's pandering sentence on condition that he did not resist deportation to Italy.

On February 2, 1946, two federal immigration agents transported Luciano from Sing Sing prison to Ellis Island in New York Harbor for deportation proceedings.

On February 10, Luciano's ship sailed from Brooklyn harbor for Italy.

This was the last time he would see the US. On February 28, after a 17-day voyage, Luciano's ship arrived in Naples. On arrival, Luciano told reporters he would probably reside in Sicily.

In October 1946, Luciano secretly moved to Havana, Cuba. Luciano first took a freighter from Naples to Caracas, Venezuela, then flew to Rio de Janeiro, Brazil. He then flew to Mexico City and doubled back to Caracas, where he took a private plane to Camaguey, Cuba, finally arriving on October 29. Luciano was then driven to Havana, where he moved into an estate in the Miramar section of the city. His objective was to be closer to the US so that he could resume control over American Mafia operations and eventually return home.

In 1946, Lansky called a meeting of the heads of the major crime families in Havana that December, dubbed the Havana Conference. The ostensible reason was to see singer Frank Sinatra perform. However, the real reason was to discuss mob business with Luciano in attendance. The three topics under discussion were: the heroin trade, Cuban gambling, and what to do about Siegel and his floundering Flamingo Hotel project in Las Vegas.

Soon after the Conference began, the US government learned that Luciano was in Cuba. Luciano had been publicly fraternizing with Sinatra as well as visiting numerous nightclubs, so his presence was no secret in Havana. The US started putting pressure on the Cuban government to expel him. On February 21, 1947, U.S. Narcotics Commissioner Harry J. Anslinger notified the Cubans that the US would block all shipment of narcotic prescription drugs while Luciano was there.

After Luciano's secret trip to Cuba, he spent the rest of his life in Italy under tight police surveillance. When he arrived in Genoa on April 11, 1947, Italian police arrested him and sent him to a jail in Palermo.

On May 11, a regional commission in Palermo warned Luciano to stay out of trouble and released him.

On June 9, 1951, he was questioned by Naples police on suspicion of illegally bringing $57,000 in cash and a new American car into Italy. After 20 hours of questioning, police released Luciano without any charges.

On November 1, 1954, an Italian judicial commission in Naples applied strict limits on Luciano for two years. He was required to report to the police every Sunday, to stay home every night, and to not leave Naples without police permission. The commission cited Luciano's alleged involvement in the narcotics trade as the reason for these restrictions.

By 1957, Genovese felt strong enough to move against Luciano and his acting boss, Costello. He was aided in this move by Anastasia family underboss Carlo Gambino. On May 2, 1957, following Genovese's orders, Vincent "Chin" Gigante ambushed Costello in the lobby of his Central Park apartment building, The Majestic. Gigante called out, "This is for you, Frank," and as Costello turned, shot him in the head. After firing his weapon, Gigante quickly left, thinking he had killed Costello. However, the bullet had just grazed Costello's head and he was not seriously injured. Although Costello refused to cooperate with the police, Gigante was arrested for attempted murder. Gigante was acquitted at trial, thanking Costello in the courtroom after the verdict. Costello was allowed to retire after conceding control of what is called today the Genovese crime family to Genovese. Luciano was powerless to stop it.

On October 25, 1957, Genovese and Gambino successfully arranged the murder of Anastasia, another Luciano ally. The following month, Genovese called a meeting of bosses in Apalachin, New York to approve his takeover of the Luciano family and to establish his national power. Instead, the Apalachin Meeting turned into a fiasco when law enforcement raided the meeting. Over 65 high-ranking mobsters were arrested and the Mafia was subjected to publicity and numerous grand jury summons.

On April 4, 1959, Genovese was convicted in New York of conspiracy to violate federal narcotics laws. Sent to prison for 15 years, Genovese tried to run his crime family from prison until his death in 1969. Meanwhile, Gambino now became the most powerful man in the Cosa Nostra.

On January 26, 1962, Luciano died of a heart attack at Naples International Airport.