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Kaline was born and raised in Baltimore, Maryland. His family was poor. Several relatives played semi-pro baseball, but no one in his family had graduated from high school. When he was eight years old, Kaline developed osteomyelitis and had a segment of bone removed from his left foot.

Kaline bypassed the minor league system and joined the Tigers directly from high school as an 18-year-old "bonus baby" signee, receiving $35,000 ($320,137 in today's dollars) to sign with the team. He made his major league debut on June 25, 1953 in Philadelphia as a late-inning replacement for outfielder Jim Delsing. Kaline wore number 25 during his rookie campaign, but asked teammate Pat Mullin for his No. 6 after the 1953 season ended. Kaline wore the number for the rest of his major league playing career. He was known simply as "Six" in the Tiger clubhouse.  In 1955, at age 20, Kaline ended the season with a .340 batting average, becoming the youngest player ever to win the American League batting title. No 20-year-old major league player had won a batting title since Ty Cobb in 1907. During the 1955 season, Kaline became the 13th man in major league history to hit two home runs in the same inning, became the youngest to hit three home runs in one game, and finished the year with 200 hits, 27 home runs and 102 RBIs. He also finished second to Yogi Berra in the American League's 1955 Most Valuable Player Award voting. He was selected to the Major League Baseball All-Star Game, the first in a string of consecutive All-Star selections that lasted through 1967.  Kaline followed in 1956 with a .314 batting average with 27 home runs and 128 RBIs. He led the league in outfield assists with 18 in 1956 and again in 1958 with 23. Kaline was out for several games in 1958 after he was hit by a pitch. He missed several games in 1959 after he was hit by a thrown ball and sustained a fracture in his cheekbone. Kaline had been knocked out from the blow and initial speculation was that he could miss six weeks of the season.
Al Kaline