Hoffa’s father was a coal miner who labored long hours to support his family and died young of a lung disease associated with working conditions in the mines. Hoffa's mother was employed as a domestic worker and a cook, and took in washing to make ends meet. She moved the family to Detroit, Michigan, four years after the death of her husband.

Jimmy Hoffa attended school until the tenth grade, when he dropped out to help his family meet the severe economic conditions of the Great Depression. He took a full-time job as a stock boy at Kroger's, a Detroit grocery store chain. The low pay, poor working conditions, and the impact of the Great Depression all contributed to making the young Hoffa conscious of workers' problems. Hoffa began to demonstrate his organizing skills as a young man. At age seventeen he led four of his co-workers in a successful strike against the Kroger Company. Hoffa's synchronized the strike with the delivery of a large trailer of fresh strawberries to the Kroger loading docks. Kroger's business managers knew it would not take long for the strawberries to spoil and they desperately needed the loading dockworkers to unload the shipment. Within one hour a new union contract was reached and within one year Jimmy Hoffa's "Strawberry Boys" joined Teamsters Local 674, which later merged with Truck Drivers Local 299. Hoffa transformed the local from a 40-member unit with $400 in its coffers to a 5000 member unit with $50,000 in the bank.

The early U.S. labor movement was volatile and Hoffa's involvement with the IBT during the late 1930s resulted in many threats to his life. Hoffa's car was bombed, his office was searched, and he was once arrested eighteen times in a single day. Hoffa once recalled, "When you went out on strike in those days, you got your head broken. The cops would beat your brains out if you even got caught talking about unions." Undeterred, at the age of twenty-eight Hoffa became vice president and chief negotiator for the IBT.

During the 1950s the federal government began promoting strong attacks against organized crime such as the Mafia. Hoffa had never made a secret of his relationship with the Mafia and the federal government's intense focus on organized crime, combined with the resistance of business to his unionizing, squeezed Hoffa at both ends. The government, for criminal reasons, and business, for labor reasons, both sought Hoffa's downfall. During the 1960s, after numerous charges of corruption in the Teamsters, Hoffa faced several felony trials. He was convicted of jury tampering and fraud in two separate trials in 1964, and was sentenced to a 15-year prison term. President Richard Nixon (19691974) commuted Hoffa's sentence in 1971, but banned him from any union activity. Hoffa had remained president of the Teamsters Union throughout the five years he served in jail, but upon his release from prison he stepped down.

Hoffa appealed to the courts to regain his union presidency but the Supreme Court denied his motion. Hoffa continued to be unofficially involved with the Teamsters union, and with organized crime. On July 30, 1975, Hoffa disappeared after a luncheon meeting. He was never seen again. His colorful life and mysterious disappearance have created an enduring historical legend about the man who served at the forefront of the U.S. labor movement in the mid-twentieth century. He was declared legally dead in 1983.

In September 2001, the FBI's interest in Hoffa's disappearance was rekindled when DNA evidence linked a strand of Hoffa's hair to a longtime friend, Charles O'Brien. The hair, found in the backseat of a car borrowed by O'Brien on the day Hoffa went missing, matched a hair taken from Hoffa's hairbrush and contradicted O'Brien's claim that Hoffa had not been in the car. Charges have never been filed in the case, but authorities are hoping to eventually have sufficient evidence to bring the case to court. O'Brien, meanwhile, denies any wrongdoing and claims to have been wrongly implicated in the disappearance.