Louis's cultural impact was felt well outside the ring. He is widely regarded as the first African American to achieve the status of a nationwide hero within the United States, and was also a focal point of anti-Nazi sentiment leading up to and during World War II. He also was instrumental in integrating the game of golf, breaking the sport's color barrier in America by appearing under a sponsor's exemption in a PGA event in 1952.

Louis was born on May 13, 1914 in a ramshackle dwelling about six miles northwest of La Fayette, in rural Chambers County, Alabama. Louis was the son of Munroe Barrow and Lillie (Reese) Barrow, and seventh of eight children. He weighed 11 pounds at birth. Both Louis's parents were the children of former slaves, alternating between sharecropping and rental farming. Munroe was predominantly African American with some white ancestry, while Lillie was half Cherokee.

Louis spent twelve years growing up in rural Alabama, where little is known of his childhood. He suffered from a speech impediment, and spoke very little until about the age of six. Munroe Barrow was committed to a mental institution in 1916, and as a result Joe knew very little of his biological father. Around 1920, Louis's mother married Pat Brooks, a local construction contractor, having received word that Munroe Barrow had died while institutionalized (in reality, Munroe Barrow lived until 1938, unaware of his son's fame).

In 1926, shaken by an altercation with the Ku Klux Klan, Louis's family moved to Detroit, Michigan, forming part of the post-World War I Great Migration. Joe's brother worked for Ford Motor Company (where Joe would himself work for a time at the River Rouge Plant) and the family settled into a home at 2700 Catherine (now Madison) Street in Detroit's Black Bottom neighborhood.

Louis attended Bronson Vocational School for a time to learn cabinet-making, and his mother attempted to get Joe interested in playing the violin.

The Depression hit the Louis family hard, but as an alternative to gang activity, Joe began to spend time at a local youth recreation center at 637 Brewster Street in Detroit. Legend has it that he tried to hide his pugilistic ambitions from his mother by carrying his boxing gloves inside his violin case.

Louis's amateur debut, probably in early 1932, came as a light-heavyweight at age 17. A legend exists that before the fight Louis, only barely literate, wrote his name so large that there was no room for his last name "Barrow" – as a result becoming known as "Joe Louis" for the remainder of his boxing career. More likely, Louis simply omitted his last name to keep his boxing pursuits a secret from his mother. After this debut (a loss to future Olympian Johnny Miller), Louis compiled numerous amateur victories – eventually winning the club championship of his Brewster Street recreation center, the home of many aspiring Golden Gloves fighters.

In 1933, Louis won the Detroit-area Golden Gloves Novice Division championship for the light heavyweight classification against Joe Biskey, later losing in the Chicago Golden Gloves Tournament of Champions. The next year, competing in the Golden Gloves' Open Division, he won the light heavyweight classification, this time also winning the Chicago Tournament of Champions. Although a hand injury forced Louis to miss the New York/Chicago Champions' cross-town bout for the ultimate Golden Gloves championship in 1934, he followed up his Chicago performance by winning the National AAU tournament in St. Louis, Missouri in April of that year. By the end of his amateur career, Louis's record was 50 wins against 4 losses, with 43 knockouts.

Louis's impressive amateur performances attracted the interest of professional promoters. Rather than sign with an established promoter, Louis agreed to be represented by a black Detroit-area bookmaker named John Roxborough. As Louis explained it in his autobiography, Roxborough convinced Louis that white managers would have no real interest in seeing a black boxer work his way up to title contention:

[Roxborough] told me about the fate of most black fighters, ones with white managers, who wound up burned-out and broke before they reached their prime. The white managers were not interested in the men they were handling but in the money they could make from them. They didn't take the proper time to see that their fighters had a proper training, that they lived comfortably, or ate well, or had some pocket change. Mr. Roxborough was talking about Black Power before it became popular.