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.

Kaline married his high school sweetheart, Madge Louise Hamilton, in 1954. He had two sons, Mark Albert Kaline (b. August 21, 1957) and Michael Keith Kaline (b. 1962). Michael played college baseball at Miami University and is the father of Colin Kaline, who had a short Minor League career and was a college coach.

In 1955, at age 20, Kaline ended the season with a .340 batting average, becoming the youngest player ever to win the American League (AL) 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 runs batted in (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, 27 home runs and a career-high 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.

In 1961, Kaline hit .324 to finish second in the AL batting race (behind teammate Norm Cash). The Tigers won 101 games, to date the third-highest win total in team history, but still finished eight games behind a New York Yankees team that was led by the home run heroics of Roger Maris and Mickey Mantle. Kaline began the 1962 season hitting .345 with 13 home runs and 38 RBIs in 35 games. On May 26 of that season, he sustained a broken collarbone while making a game-ending catch on a ball hit by New York’s Elston Howard. He missed 57 games due to the injury and Detroit was unable to seriously compete for a pennant due to his absence. When healthy, Kaline was great in 1962, hitting 29 home runs and driving in 94 runs in only 100 games.

By late March 1963, Kaline said that he felt good and he was hitting .373 in 53 spring training at-bats. In the 1963 regular season, Kaline hit .312 with 27 home runs and 101 RBIs, finishing second to Elston Howard in the American League’s Most Valuable Player Award voting. Kaline experienced pain in his left foot, the one that had been affected by osteomyelitis as a child, throughout the 1964 season. His batting average dropped to .293 that season. Kaline tried to ignore the pain, but he saw physicians who thought he was suffering from gout and administered injections.

In the summer of 1967, the normally calm Kaline broke a bone in his hand when he struck a baseball bat against a bat rack. Kaline missed a month of play. When he returned, the Tigers were in a four-team pennant race, but the team finished a game out of first place. Kaline missed two months of the 1968 season with a broken arm, but he returned to the lineup when Tiger manager Mayo Smith benched shortstop Ray Oyler and sent center fielder Mickey Stanley to play shortstop to make room for Kaline in the outfield. ESPN later called Smith’s move one of the ten greatest coaching decisions of the century. In the 1968 World Series, the St. Louis Cardinals won three of the first four games of the series and were leading Game 5 by a score of 3–2 in the seventh inning, when Kaline hit a bases loaded single to drive in two runs. The Tigers won that game, and then won Game 6 in a blowout. Kaline had two hits, two runs scored and three RBI in the Tigers’ 10-run third inning of Game 6. Detroit went on to win Game 7 for their first world championship since 1945. In his only World Series appearance, Kaline hit .379 with two home runs and eight RBIs in seven games. For their victory, Kaline and his teammates each received bonus checks of $10,000 (at a time when Kaline’s salary was “about $70,000”).

In 1970, Kaline was nearly a victim of a freak accident on the baseball field. In a game at Milwaukee’s County Stadium on May 30, against the Milwaukee Brewers, Kaline collided with center fielder Jim Northrup as they both pursued a fly ball. Kaline fell to the warning track injured. Alertly, left fielder Willie Horton rushed over and quickly recognized that Kaline was turning blue. Horton reached in and cleared Kaline’s airway, saving his life.

Cherry Street, which ran behind the left-field stands at Tiger Stadium, was renamed Kaline Drive in his honor in 1970. On September 27, 1999, when Detroit played its last game at Tiger Stadium against the Kansas City Royals, Kaline was invited to appear in uniform and present the last lineup card to the umpires. He did so along with George Brett, the Kansas City Royals’ great and eventual Hall of Famer.

After hitting .294 in 1971, Kaline became the first Tiger to sign a $100,000 ($631,306 in today’s dollars) contract. He had turned down a pay raise from $95,000 to $100,000 the previous year, saying he did not feel like he deserved it after hitting .278 with 16 home runs in 1970. Detroit contended all season for the 1972 pennant, trailing the Red Sox by a half-game before a series against them to end the regular season. Kaline batted eight times in two games, registering five hits and three runs scored. Detroit won those first two games and clinched the AL East pennant. They lost the 1972 American League Championship Series to the Oakland Athletics that year after Reggie Jackson stole home in the final game of the series. In March 1973, Kaline won the Roberto Clemente Award in recognition of the honor he brought to baseball on and off the field.

On September 24, 1974, Kaline became the 12th player in MLB history to reach the 3,000 hit milestone, when he hit a double off the Orioles’ Dave McNally. After reaching the milestone, Kaline announced that he would retire. “I’m glad it’s over. I really am. I don’t think I’ll miss it. I may miss spring training”, Kaline said after his last game on October 3, 1974.

Kaline was elected to the Baseball Hall of Fame in 1980, becoming the tenth player in history to be inducted in his first year of eligibility. He was named on 340 of the 385 ballots (88.3%) cast by sportswriters. Kaline and Duke Snider were the only candidates elected by the sportswriters in 1980. Kaline later said, “I really never thought I would choose an individual thing that happened just to me over a team thing like the World Series. But I would have to say this is the biggest thing that has ever happened to me.”

The 1993 Major League Baseball All-Star Game was dedicated to Kaline on the occasion of the 35th anniversary of his hometown’s only other Midsummer Classic. Kaline, along with Leon Day and former Baltimore Orioles star Brooks Robinson, threw out the ceremonial first pitch to end the pregame ceremonies. Kaline’s ceremonial first pitch was caught by future Detroit Tiger Ivan Rodriguez, who was starting his All-Star debut.

Kaline was honored by the Tigers as the first of their players to have his uniform number (6) retired. Versatile and well-rounded, he won ten Gold Glove Awards (1957–59 and 1961–67) for excellence in the field and appeared in the All-Star game 15 times (1955–67, 1971, 1974). In 1998, Kaline ranked Number 76 on The Sporting News list of the 100 Greatest Baseball Players, and was nominated as a finalist for the Major League Baseball All-Century Team.

After his playing career, Kaline lived in the Detroit area, and he remained active within the Tigers organization, serving first as a color commentator on the team’s television broadcasts (1975–2002) mostly with play by play announcer and former Tiger and fellow Hall of Famer George Kell, and then later as a consultant to the team. Starting in 2003, Kaline served as a special assistant to Tigers President/CEO/General Manager Dave Dombrowski, and his duties included coaching/mentoring outfielders during spring training. Former Tigers teammate Willie Horton also holds this position, and the two threw out the first pitch of the 2006 World Series at Comerica Park. Kaline continued in his assistant role until his death in 2020. His 67 years with one team was one of the longest tenures in MLB history.

Because of his lengthy career and longtime association with the Tigers organization, Kaline’s nickname was “Mr. Tiger.” Kaline’s grandson Colin Kaline was selected by the Tigers in the 25th round of the 2007 MLB draft. He did not sign, choosing to play baseball at Florida Southern College. The team drafted him again in the 2011 MLB draft, this time in the 26th round. He played in the low minor leagues with the Detroit organization in 2011–12.

Kaline bypassed Minor League Baseball and joined the Tigers directly from high school as an 18-year-old “bonus baby” signee, receiving $35,000 ($334,459 in 2020 dollars) to sign with the team. The Detroit scout who had tracked him through high school, Ed Katalinas, said “To me he was the prospect that a scout creates in his mind and then prays that someone will come along to fit the pattern.”

Kaline died in his home in Bloomfield Hills, Michigan, on April 6, 2020; the cause of death was not reported.