A native of Greensboro, North Carolina, Ferrell was part of a baseball family. In addition to his older brother Rick, a Hall of Fame catcher, his youngest brother George was a 20-year minor league veteran.
Ferrell won 20 games six times in his ten full seasons before arm trouble ended his career at age 33. Most notably, he is the only pitcher since 1900 to win 20 games in his first four full major league seasons. He also was the MVP runnerup with the Boston Red Sox after leading the American League in wins (25), innings pitched (322-1/3) and complete games (31), while hitting .347. Widely considered the best-hitting pitcher of the 20th century, he hit .280 lifetime and set records for home runs in a season (9) and a career (38). He retired with the seventh highest winning percentage (.601) among pitchers with at least 300 AL decisions (for teams that never won the pennant) and also with the fourth highest fielding percentage (.975) in AL history. His brother Rick was his batterymate for five seasons.
The season was Ferrell's best yet. On April 29, he pitched a 9-0 no-hitter against the St. Louis Browns, striking out eight, and hit a home run with a double and four runs batted in. His brother Rick, catching for the Browns, came the closest to getting a hit, reaching base on an error by the shortstop. Then, on August 31 Ferrell hit two home runs as he beat the Chicago White Sox 13–5 at Comiskey Park. Winner of 13 consecutive games, he finished the year at 22-12 with 123 strikeouts, a 3.75 ERA, and an AL-best 31 complete games, at times also terrorizing his rivals with the bat. Ferrell matched the opponents' batters homer-by-homer; they hit nine home runs off him, but he also smashed nine balls out of the park.
In Ferrell posted his fourth consecutive 20-win season, with a record of 23-13, 105, 3.66. However, he had a foul temper, and because of his volatile character he was fined and suspended many times for refusing to leave a game, or for leaving it without permission. After being driven from the mound in one game, he destroyed the clubhouse, punched himself in the jaw so hard that he nearly knocked himself out, and tore his uniform to shreds. Ferrell was named to the first AL All-Star team in , but with his pitching skill diminished by shoulder pain, and after a disappointing 11-12 record in the year, he was sent to the Boston Red Sox, where his brother Rick – whose personality was almost the opposite of Wes' – was a fine all-around catcher. Ferrell recovered his form in with a 14-5 mark, also hitting two home runs in a 10-inning, 3–2 victory for Boston over the White Sox. It was the second time that season he had a pair of home runs in a single game, and the third time in his career. In all, he would homer twice in a game six times. In the same season, Ferrell was pitching when Babe Ruth made his farewell appearance in Boston at Fenway Park on August 12, drawing a record crowd of 46,766 fans (with about 20,000 turned away). Ruth singled and doubled against Ferrell, but the New York Yankees lost 6–4.
In Ferrell won a league-high 25 games, as his .347 batting average was only two points lower than that of AL batting champion Buddy Myer, then, in he went 20-15. During the 1937 midseason, the Ferrell brothers and Mel Almada were sent to the Washington Senators in the same trade that brought Ben Chapman and Bobo Newsom to Boston. Wes made his second All-Star team shortly afterward as he led the AL in innings and complete games each season from 1935 to 1937. After being released by Washington in despite a 13-8 record, Ferrell was signed by the Yankees, but he never came back after arm surgery over the winter. He was released in May 1939.
Ferrell won 190 games between 1929 and 1938. He made one relief appearance for the Brooklyn Dodgers in 1940, and ended his career with four games for the Boston Braves in 1941. His final record was 193-128, with a 4.04 ERA and 985 strikeouts in 374 games and 3623 innings.
In addition to his talent as a pitcher, Ferrell was also one of the best-hitting pitchers in major league history, setting records for pitchers for most home runs in a season with nine, in , and 37 for a career – his total of 38 homers (37 as a pitcher, 1 as an outfielder) were ten more than Rick had in over five times as many at bats. Ferrell also tied the AL record held by Pete Appleton and George Uhle with six RBI in a single game, and five times hit two home runs in one game. In all, he collected 329 hits, 57 doubles, 13 triples, 208 RBI, 175 runs, 129 hit by pitches, and a .446 slugging percentage, as he drew a fair number of walks (129), resulting in a .351 career on base percentage. In 1933, his last season with the Cleveland Indians, he played the last 13 games of the season as an outfielder.
"I didn't see any big deal in being a good hitter as well as a good pitcher," said Ferrell, a two-time minor league batting champion as an outfielder after his major league days were over. When he went on to be a manager, Ferrell was slapped with suspensions for belting an umpire, and for removing his team from the field. He was a fiery competitor and a brilliant player with natural talent, whose achievements may have been obscured by his irascibility.
Wes Ferrell died in Sarasota, Florida at 68 years of age. Although he, unlike his brother, has not been inducted into the Baseball Hall of Fame, in 1981, Lawrence Ritter and Donald Honig included him in their book The 100 Greatest Baseball Players of All Time, in celebration of his being not just a star pitcher but the best-hitting pitcher of all time -- noting that Babe Ruth did most of his hitting when he was no longer a regular pitcher.
In February , Ferrell was inducted to the Boston Red Sox Hall of Fame. In August, he was named as one of the ten former players that began their careers before 1943 to be considered by the Veterans Committee for induction into the National Baseball Hall of Fame in 2009.