Louis Buchalter was born on February 6, 1897, in Manhattan's Lower East Side. He came from a large Ashkenazi Jewish family. His parents immigrated separately from the Russian Empire and married in New York in 1893. They had three sons together. His mother lovingly called him "Lepkeleh," which means "little Louis" in Yiddish. This nickname later became "Lepke."

Buchalter's father, Barnett (also called Berl), was a widower from Pruzhany, now in Belarus. He moved to the United States in 1890 with his three daughters. He worked as a machinist and also operated a hardware store. His mother, Rose (Reisel) Kauvar Buchalter, originally from Vilnius, was previously married and had three sons and two daughters. Louis had several siblings, including his half-brother, Rabbi Charles Kauvar, and brothers Emanuel and Isadore, who became a dentist and pharmacist, respectively.

Tragedy struck when Buchalter was just 12 years old; his father died in 1909. In 1910, he completed elementary school and began selling theatrical goods. He attended the Rabbi Jacob Joseph School on the Lower East Side and was noted to be an honor roll student. Soon after, his mother moved to Arizona for health reasons, leaving Louis under the care of his sister, Sarah. However, he proved to be uncontrollable for her.

Buchalter's first arrest occurred on September 2, 1915, for burglary and assault, but the case was dismissed. Later in late 1915 or early 1916, he moved in with his uncle in Bridgeport, Connecticut. Unfortunately, he was arrested again on February 29, 1916, for burglary and sent to the Cheshire Reformatory for juvenile offenders until July 12, 1917. After a disagreement with his uncle regarding wages, he returned to New York City.

On September 28, 1917, Buchalter faced an 18-month prison sentence in Sing Sing for grand larceny. After being moved to Auburn Prison, he was released on January 27, 1919. However, he was back in Sing Sing on January 22, 1920, for a 30-month sentence for attempted burglary, only to be released again on March 16, 1922.

Following his release, Buchalter began working with his childhood friend, Jacob "Gurrah" Shapiro.

On May 9, 1941, Louis Buchalter was arraigned in New York state court for the murder of Joseph Rosen, which took place in 1936, along with three other murders. The authorities had gathered information from mobster Abe Reles, who became a witness against Buchalter in 1940 and claimed that he had ordered the hit on Rosen. During the trial, additional testimony was given by Albert "Tick-Tock" Tannenbaum. After four hours of deliberation, the jury found Buchalter guilty of first-degree murder at 2 am on November 30, 1941.

On December 2, 1941, Buchalter was sentenced to death, along with his associates Emanuel "Mendy" Weiss and Louis Capone. His legal team quickly filed an appeal against the conviction. In October 1942, the New York Court of Appeals upheld his conviction and death sentence by a narrow margin, with several dissenting judges arguing that the evidence against him was weak.

Buchalter's lawyers sought further review from the United States Supreme Court. In 1943, the Supreme Court affirmed the conviction with a unanimous decision. This left Buchalter with no more legal options for appeal.

After the Supreme Court's decision, Buchalter was still serving a separate sentence for racketeering at Leavenworth Federal Prison. New York authorities then requested that he be handed over for execution. On January 21, 1944, he was transferred to Sing Sing prison. Despite making several pleas for mercy, these requests were denied.

On March 4, 1944, Louis Buchalter was executed in the electric chair at Sing Sing. He did not speak any final words. Just minutes before his execution, his lieutenants Weiss and Capone were also put to death. Buchalter was buried at Mount Hebron Cemetery in Queens, New York.