He made the Tigers team in spring training 1945 before finishing high school and without having played in the minor leagues, but sat on the bench before making his major league debut in June 1945, just a few weeks after his 18th birthday. He made three relief appearances that month and two more in September after a two-month stint with the Buffalo Bisons of the International League under manager Bucky Harris, and was on the Detroit roster for the team's victory in the 1945 World Series although he did not appear in any games. He had a remarkably unassuming presence; Paul Richards, then a catcher for the Tigers, later recalled occasionally going to his neighborhood drugstore. One day, Pierce went up to him at practice and asked why Richards never talked to him at the store, with Richards replying that he didn't know what Pierce was talking about; Pierce answered that the drugstore was his family's, and Richards slowly realized that Pierce had been the clerk behind the counter each time he went in.  Pierce was sent back to Buffalo for the 1946 season, now with Gabby Hartnett as his manager (Harris having moved to the team's front office), but missed most of the year with a back injury which was attributed to overwork. After the 1947 season in Buffalo, where Richards was now his manager, he returned to Detroit in 1948, spending most of the season in the bullpen but making five starts and posting a 3–0 record; he had yet added very little weight since his high school days, being still at 148 pounds. He made his first start, and earned his first major league victory, on August 8 against the Washington Senators, pitching 7⅔ innings and striking out six in a 6–5 victory in which he also drove in a run with a triple and scored. However, Pierce also issued 51 walks in 55⅓ innings that year, and concerns about his pitching control led the Tigers to trade him to the White Sox on November 10 for catcher Aaron Robinson and $10,000, in what most baseball historians consider to be one of the most one-sided trades in baseball history. Talks had initially centered on Chicago acquiring Pierce's high school teammate Ted Gray, although sources differ as to whether it was White Sox general manager Frank Lane or his Detroit counterpart Billy Evans who switched the focus to Pierce; the Tigers tried to call off the deal one day after it was completed upon fully realizing what they had given up, even offering $50,000 to get Pierce back, but Lane had no intention of giving up the steal he had accomplished in his first trade as general manager.