Freehan attended the University of Michigan, where he set an all-time Big Ten Conferencebatting mark of .585 in 1961 and also played football. He signed with his hometown Tigers in 1961 for a $100,000 bonus, which his father withheld until he graduated in 1966, and broke in briefly with 4 games at the end of the season before returning to the minors in 1962. In 1963 he arrived in the majors to stay, working with former catcher Rick Ferrell on his defense and splitting catching duties with Gus Triandos, who was traded following the season. The 1964 campaign gave indications of what was to come; he batted .300 to finish sixth in the American League (AL), along with 18 home runs and 80 runs batted in. He also earned the first of ten consecutive All-Star selections, and placed seventh in the Most Valuable Player Award balloting. In 1965 he led the AL in putouts for the first of six times, and received his first of his five consecutive Gold Gloves. In 1966 he again led the league in putouts, and also led in fielding percentage for the first of four times.
He had an even better year in 1968 as he was considered the quiet leader of the 1968 World Series championship squad, posting career highs with 25 home runs and 84 RBI, fifth and sixth in the AL respectively. Freehan broke his own records with 971 putouts and 1,050 total chances, marks which remained league records until Dan Wilson topped them with the 1997Seattle Mariners. He was also hit by 24 pitches, the most in the AL since Kid Elberfeld in 1911. Despite playing in hitter-friendly Tiger Stadium, Freehan guided the Tigers' pitching staff to an earned run average of 2.71, third best in the league. McLain won 31 games and Lolich won 17 as the Tigers ran away with the pennant. Because of his offensive and defensive contributions, he finished second to McLain in the MVP voting. Freehan and Carl Yastrzemski were the only players to finish in the top ten of the voting in both 1967 and 1968, and only Yastrzemski reached base more often in 1968. He capped his season by recording the final out of the World Series against the St. Louis Cardinals, retiring Tim McCarver on a popup. He also made a pivotal play in Game 5, with the Cardinals leading the Series 3-1 and the game 3-2. In the fifth inning, Lou Brock – whom Freehan had thrown out on an attempted steal in the third inning – doubled with one out and attempted to score on Julián Javier's single, but Freehan successfully blocked the plate with his foot, and held on to the ball even though Brock came in standing up in an attempt to knock the ball loose. Detroit won by scoring three runs in the seventh inning, and went on to take the last two games.
Although his later seasons rarely approached the brilliance of those two campaigns, he continued to turn out All-Star years for the Tigers. In 1971 he batted .277 with 21 home runs, and he hit .262 for the 1972Eastern Division champions. He missed the first two games (both losses) of the 1972 American League Championship Series against the Oakland Athletics while recovering from a hairline fracture of his thumb, then doubled and homered in a 3-0 Game 3 win, in which Joe Coleman set a League Championship Series record with 14 strikeouts. Freehan drove in the first of three runs in the tenth inning of Game 4 in a memorable 4-3 come-from-behind victory which tied the series; he also drove in Detroit's only run in the 2-1 Game 5 loss. In 1974, playing primarily at first base, he finished fifth in the American League in slugging average with a .479 mark. He moved back behind the plate the following year to earn his eleventh All-Star berth. Freehan ended his career in 1976, batting .270.
In his 15-year career, Freehan played in 1,774 games with 1,591 hits in 6,073 at bats for a .262 batting average along with 241 doubles, 200 home runs, 758 RBI, and a .340 on-base percentage. In addition to his home runs and total bases, his .412 slugging average and totals of 1,591 hits, 706 runs and 476 extra base hits all put him among the top five AL catchers to that time. His batting totals are particularly remarkable in light of the fact that offense was at a low throughout the sport during his career, with a decided advantage toward pitchers. Freehan led all AL catchers in fielding percentage four times (1965, 1966, 1970, 1973). He also ranked sixth in American League history with 114 times being hit by a pitch. Freehan caught more games than any other player in Tigers' team history. In his book, The Bill James Historical Baseball Abstract, baseball historian Bill James ranked Freehan 12th all-time among major league catchers.
In 1969, Freehan penned "Behind the Mask", a diary-type recording of his thoughts and experiences as seen from the catcher's perspective. After retiring, he coached Tigers catcher Lance Parrish on the fine points of playing his position. In 1978, Freehan was one of seven members of the inaugural class of inductees to the University of Michigan Athletic Hall of Honor. He served as a color commentator for Seattle Mariners broadcasts in 1979–80, and for Tigers broadcasts on PASS Sports television in 1984–85, and returned to the University of Michigan as head coach of the baseball team from 1989 to 1995.