He was signed by the Detroit Tigers in 1939 at the age of 18. A Tigers scout offered a $500 signing bonus to Newhouser, who found the sum of money to be unimaginable. Ten minutes after he signed, someone arrived from the Cleveland Indians; that employee had been prepared to offer $15,000 to his parents in addition to a $4,000 car.

Newhouser made his debut for Detroit on September 29, 1939. In 1940, he earned a spot on the Tigers out of spring training. In his first two full big-league seasons, the young left-hander experienced control problems, walking more batters than he struck out while posting win-loss records of 9–9 and 9–11. He improved in 1942 and 1943, posting excellent earned run averages (ERAs), but he still lost more than he won on a team with a weak offense.

He blossomed in 1944, becoming a dominant pitcher in wartime baseball. That season, Newhouser rang up a 29–9 record, leading the league in wins and strikeouts (187). His 2.22 ERA was second in the league, as were his 25 complete games and six shutouts. The Tigers jumped into contention, finishing second in the American League, with Newhouser named MVP. Newhouser won the first Sporting News Pitcher of the Year Award in 1944.

By the 1945 season, Newhouser had been selected for three consecutive AL All-Star teams. The 1945 All-Star Game was cancelled on April 24 because of travel restrictions and seven out of eight scheduled interleague games were played in place of the All-Star Game on July 9 and 10 to support the American Red Cross and War Relief fund. Newhouser became the first pitcher to repeat as MVP that season and helped the team win the World Series. He won the pitcher’s Triple Crown, leading the AL in wins (25, against nine losses), ERA (1.81) and strikeouts (212); he also led the league in innings pitched, games started, complete games and shutouts. Newhouser pitched four innings of relief on the season’s final day as Detroit rallied for the pennant. Newhouser won the second Sporting News Pitcher of the Year Award. He became the youngest player (24) to win the award in two consecutive years. In that year’s World Series, Newhouser won two games, including a complete-game victory in the deciding seventh game.

In 1946, he went 26–9 with a 1.94 ERA, again leading the league in wins and ERA. His 275 strikeouts was second in the league. Newhouser was runner-up in the MVP race to Ted Williams. Newhouser continued to rate among the game’s best pitchers for the next five years. He won 17 games in 1947, led the AL with 21 wins in 1948 and rang up an 18–11 mark in 1949. After a 15–13 season in 1950, he hurt his arm and his workload was cut significantly.

After being released by the Tigers following the 1953 season, Newhouser signed on with the Cleveland Indians and was their top long reliever in 1954, when Cleveland won 111 games and the pennant. In his final big-league hurrah, he posted a 7–2 mark with a 2.54 ERA, and got to pitch in his second World Series. He ended his career with a record of 207–150 and a 3.06 ERA. He is the only pitcher ever to win consecutive MVP awards.

Eventually, he served as a scout for the Baltimore Orioles, Cleveland Indians, Detroit Tigers, and Houston Astros. As a scout with the Orioles, Newhouser discovered Milt Pappas, a Detroit high schooler who went on to win 209 games in an All-Star career — two more than Newhouser did. He also signed future Cy Young Award winner Dean Chance, who later earned the trophy with the Los Angeles Angels in 1964.

In 1992, he was elected to the National Baseball Hall of Fame. His induction class included Tom Seaver, Rollie Fingers and Bill McGowan. The ceremony was attended by a then-record-setting crowd of 20,000 people. The Tigers retired Newhouser’s number 16 in 1997. He died on November 10, 1998 in a hospital in Southfield, Michigan. He had been ill with emphysema and heart problems.