McLain attended Mt. Carmel High School in Chicago, and played shortstop and pitcher. Originally signed by the Chicago White Sox, he was selected off waivers by the Detroit Tigers, with whom he broke into the major leagues at the age of 19 in 1963. His debut on September 21 (against the White Sox) was a success: not only did beat the Sox, holding them to one earned run on seven hits, but he picked two runners off base and even hit a home run, the only one he would ever hit in majors. After a mediocre 1964 (McLain was still only twenty), he broke through in 1965, posting a 2.61 ERA and a 16-6 record. He would remain one of the top pitchers in Major League Baseball through 1969.