Armed with a blazing fastball and a hard-nosed attitude, during his career he was identified as one of the most intimidating pitchers in the game. Wynn once admitted that if he was in a tight situation, with men in scoring position and the game in the balance, he would deck his own mother if she was the batter.

Early Wynn was born in Hartford, Alabama. His durability helped him lead the American League in innings three times (1951, 1954, 1959) and propelled him to an AL record for most years pitched (23). Wynn won an even 300 games, highlighted by five 20-win seasons, 2,334 strikeouts, 290 complete games, 49 shutouts, and 4,556 innings pitched in 691 games.

In a book titled "Spirit of St. Louis" by Peter Golenbock, a former St. Louis Browns player named Ellis Clary was recapping his career and mentioned that he was playing for the Birmingham Barons, an independent team in the Southern League, a 17-year old Early Wynn showed up for a tryout in Florida in a T-shirt, a pair of blue jeans and a Coca-Cola cap. He said he could play; they said, "We'll find out."

Wynn signed with the Senators at age 17, and after only three appearances in 1939 he blossomed in 1941, winning 72 games before being dealt to Cleveland in December 1948. The Indians' pitching coach and former star pitcher Mel Harder, taught him how to throw a curveball, slider, changeup and knuckleball. Wynn assimilated Harder's lessons easily, and after his '49 season adjustment, the next year he won 18 games and led the AL with a 3.20 ERA. In 1950 he had his first 20-win season. By this time he had become part of a strong pitching staff, forming – with Bob Feller, Bob Lemon and Mike Garcia – one of the greatest pitching rotations in baseball history. Wynn was traded to the White Sox after the '57 season. In 1954, he posted a 2.73 ERA, won 23 games and struck out 155 batters.

In 1958 Wynn became the first major league pitcher to lead his league in strikeouts in consecutive years with different teams (184 with Cleveland, 189 with Chicago), and he won the Cy Young Award in 1959 at the age of 39, posting a record of 22–10, with 179 strikeouts and a 3.16 ERA to lead the Sox to the pennant.

In this decade Wynn had more strikeouts (1,544) than any other pitcher in the majors, and he was capable with the bat as well. A dangerous switch hitter, Wynn hit .270 or better five times, and in his career batted .214 (365 for 1704), with 17 home runs and 173 RBI, with 90 pinch-hit appearances including a grand slam, making him one of five MLB pitchers to clear the bases as a pinch-hitter.

Widely known as a pitcher with a mean disposition (or at least as a pitcher who cultivated that image), Wynn threw at batters frequently enough to be labeled a "headhunter." When asked if he would throw at his own grandmother, he said, "I'd have to. My grandma could really hit the curveball." According to Rod Carew, he learned when Wynn came to Minnesota as a coach, his competitiveness didn't end when his career did. "Early would knock you down in batting practice. If you hit a ball good off of him, he'd knock you down and then challenge you. He told you to expect it when you stepped in the cage against him.

Early Wynn returned to Cleveland in 1963 for a last run. In that season, he won his 300th game, after failing to collect the milestone win in seven starts over nine months in 1962–63. Both the timeframe and the number of attempts are the longest between any pitcher's 299th and 300th wins in history. At the end of his career, Wynn had simply lost his stuff. Opposing Kansas City batter Ed Charles recalled Wynn's 300th win: "His fastball, if it reached 80, that was stretching it. He was laboring, throwing nothing but bloopers and junk." Nonetheless, Wynn left the game after five innings, and the bullpen preserved the victory, Wynn's last. Said Wynn, "I was exhausted."

Upon his retirement in 1963, Wynn was the last major leaguer to have played in the 1930s to still be playing. Wynn became the pitching coach for the Indians in 1964, where he coached Sam McDowell, Sonny Siebert, Luis Tiant, Steve Hargan, and others, who were to set the American League team record for strikeouts in a season in 1967.

Wynn was the pitcher who allowed the most home runs in Mickey Mantle's career (13). From 1977 to 1980, he provided the color commentary for radio broadcasts of Toronto Blue Jays games, working alongside Tom Cheek. He also provided color commentary for Chicago White Sox radio broadcasts for a while.