Lombardi was born on June 11, 1913, in the Sheepshead Bay neighborhood of Brooklyn to Enrico "Harry" Lombardi (1889–1971) and Matilda "Mattie" Izzo (1891–1972). Harry's mother and father, Vincenzo and Michelina, emigrated from Salerno, Italy. Mattie's father and mother, Anthony and Loretta, emigrated from Vietri di Potenza, Basilicata. Harry had three siblings, and Matilda had twelve. Vince would be the oldest of five children, Madeleine, Harold, Claire, and Joe. The entire Lombardi and Izzo clan settled in Sheepshead Bay.
Matilda's father, Anthony, opened up a barber shop in Sheepshead Bay before the turn of the century. At about the time of Lombardi's birth, Harry, and his brother, Eddie, opened a butcher shop in the Meatpacking District of Manhattan. Throughout the Great Depression, Harry's shop did well, and his family prospered. Lombardi grew up in an ethnically diverse, middle-class neighborhood.
Church attendance was mandatory for the Lombardis on Sundays. Mass would be followed with an equally compulsory few hours of dinner with friends, extended family members, and local clergy. Lombardi himself was an altar boy at St. Mark's Catholic Church. Outside their local neighborhood, the Lombardi children were subject to the rampant ethnic discrimination that existed at the time against Italian immigrants and their descendants. As a child, Lombardi helped his father at his meat cutting business, but grew to hate it. At the age of 12 he started playing in an uncoached but organized football league in Sheepshead Bay.
Lombardi graduated from the eighth grade at P.S. 206 at age 15 in 1928.[note 1] He then matriculated with the Cathedral Preparatory Seminary (Queens) a part of Cathedral College of the Immaculate Conception in Brooklyn, a six-year secondary program to become a Catholic priest. At Cathedral, he played on the school's baseball and basketball teams, but his performance was hindered by his poor athleticism and eyesight. Against school rules, he continued to play football off-campus throughout his studies at Cathedral. After completing four years at Cathedral he decided not to pursue the priesthood. He enrolled at St. Francis Preparatory high school for the fall of 1932.[note 2] There he became a Charter Member of Omega Gamma Delta fraternity. His playing as a fullback on the Terriers' football team earned him a spot on the virtual All-City football team.
In 1933, Lombardi received a scholarship to Fordham University in the Bronx to play for the Fordham Rams and Coach Jim Crowley, who was one of the of in the 1920s. During his freshman year, Lombardi proved to be an aggressive and spirited player on the football field. Prior to the beginning of his sophomore year, Lombardi was projected to start games at the tackle position. Lombardi was only 5'8" and about 180 pounds and was classified as undersized for the position
In his senior year of 1936, he was the right guard in the Seven Blocks of Granite, a nickname given by a Fordham University publicist to the Fordham University football team's offensive front line.[note 3] In a game against , he suffered a severe gash inside his mouth and had several teeth knocked out. He missed most of the remainder of the game, until he was called in on defense for a successful goal line stand that preserved a 0–0 tie. The Rams were 5–0–2 before losing in the final game of the season, 7–6, to NYU. The loss destroyed all hopes of Fordham playing in the Rose Bowl and taught Lombardi a lesson he would never forget — never to underestimate your opponent.
Lombardi graduated from Fordham University on June 16, 1937. The economic outlook of the Great Depression offered him few opportunities for a career. For the next two years, he showed no discernible career path or ambition. He tried his hand at semi-professional football with the Wilmington Clippers of the and as a debt collector, but those efforts very quickly proved to be failures. With his father's strong support, he enrolled in Fordham Law school in September 1938. Although he did not fail any classes, he believed his grades were so poor that he dropped out after one semester. Later in life, he would explain to others that he was close to graduating, but his desire to start and support a family forced him to leave law school and get a job. He would also join the Brooklyn Eagles.