Born in Palermo, Sicily, Lucchese immigrated to the United States some time during the first decade of the 20th century. He lost a finger following an industrial accident in 1915 and a police officer during one of his earlier bookings made a comment regarding Luchese's deformed hand Mordecai "Three-Finger Brown" Brown, a popular baseball player of that era who also had a deformed hand, thus earning Luchese his nickname, but not one used by his associates. Lucchese started his own window cleaning company when he was 18 working with Samuele Magliocco, which eventually became an extortion racket. As a young man, he racked up a long list of arrests including some for homicide. However, except for a single grand larceny charge, he managed to avoid conviction in every case.
In 1930, the Castellammarese War was being fought between two rival crime bosses, Guiseppe "Joe the Boss" Masseria and Salvatore Maranzano. Lucchese began the war as the right-hand man of Gaetano "Tom" Reina, the head of a family aligned with Masseria. In February 1930, Vito Genovese, a Masseria gunman, killed Reina. Masseria had suspected Reina of plotting with Maranzano and decided to replace him with a more controllable ally, Joseph Pinzolo. Lucchese resented Pinzolo's appointment and allegedly murdered him. Luckily for Lucchese, Masseria attributed the killing to Maranzano.
As the gang war continued for several years, the tide began to turn against Masseria. Charles "Lucky" Luciano, one of Masseria's top lieutenants, began secret negotiations with Maranzano. Luciano persuaded Lucchese and Gaetano "Tommy" Gagliano, another Masseria backer, to secretly switch to Maranzano. At this point, Maranzano believed that Lucchese and Galiano were now his men, but in actuality their loyalty was only to Luciano. Lucchese became one of Luciano's favoured hitmen and was alleged to have been involved in at least 30 murders.
On April 15, 1931, with the connivance of Luciano, Joe Masseria was assassinated at a restaurant in Coney Island by Genovese and several of his own men. With Masseria's death, the Castellammarese War was over and Maranzano was the victor.
With the end of the gang war, Maranzano set up a new structure of crime families that would incorporate all the existing Sicilian and Italian gangs in the United States with him as the top boss. The old Reina gang would become one of the five crime families of New York City. Gagliano became the boss of this new family with Lucchese as his underboss.
On September 10, 1931, Maranzano was murdered in his office. Jealous of their power, Maranzano had arranged the murders of Luciano and Genovese. However, Luciano found out about the plot and killed Maranzano first. Rather than become a new boss of all bosses, Luciano instead set up a Mafia Commission composed of family representatives who would regulate organized crime and prevent future wars. However, behind the scenes, Luciano was the strongest, and most respected, boss.
Gagliano remained family boss until his death by natural causes in 1953. Having served for 22 years as a loyal underboss to Gagliano, Lucchese finally took control of the organization himself. Concentrating on the core Cosa Nostra values of making money and not getting caught, Lucchese took the family into new rackets in Manhattan's Garment District and in the related trucking industry, taking control of key union officials and trade associations.
Lucchese led a quiet, stable life until he developed a fatal brain tumor and died at his home in the Lido Beach area of Long Island on July 13, 1967. His funeral at the Calvary Cemetery in Queens, New York, was attended by over 1,000 mourners, including politicians, judges, policemen, racketeers, drug pushers, pimps, and hitmen. He was succeeded as boss by Carmine Tramunti and later Antonio "Tony Ducks" Corallo.