Klein was the top hitter in Phillies' history until the arrival of Hall of Famer Mike Schmidt. He became an instant success as the starting right fielder and left-handed hitting slugger for the lowly Phillies team. A conscientious worker and hustler, Klein captured four home run championships, two RBI titles, and a batting title for the Phillies. Unlike most sluggers, Klein was a competent baserunner, topping the senior circuit in 1932 in stolen bases and had 15 triples, good for third in the league. The same year he converted in the last player to lead in homers and steals in the same season, when he paced the National League with 38 and 20. Jimmy Sheckard and Hall of Famer Ty Cobb are the only other players to do so in the majors. After the season, he was named the NL MVP.

Along with his batting prowess, the strong right-armed Klein was also a superb defensive right fielder who still holds the single-season mark with 44 assists in 1930.

In 1933 Klein won the Triple Crown (.368, 28, 120), though Carl Hubbell took MVP honors. On July 6 of that year, he also became the first Phil ever to bat in an All-Star Game.

Traded to the Cubs for the 1934 season, Klein was a disappointment in Chicago by his previous standards. Even so, he hit 20 and 21 HR in two seasons and batted .301 and .293. The Phillies reacquired him two years later.

On July 10, 1936, Klein became the first NL player to slug four home runs in a game in the 20th century. He's one of only a dozen players in baseball history to accomplish that.

Klein went to the Pirates during the 1939 season, but was back in Philadelphia the following season. For the last five years of his career, he was a part-time player, often used as a pinch-hitter. He retired after getting one hit in seven at-bats in 1944.

In his 17-year career Klein batted .320, with 398 doubles, 1201 runs batted in, 1168 runs, 1168 hits (870 extra-bases), and 300 home runs. After retiring, he ran a bar in Philadelphia for a time. He endured some tough financial times and after suffering a stroke, he returned to his home town.

Chuck Klein died in Indianapolis, Indiana at 53 years of age. He was elected to the Baseball Hall of Fame in 1980.

The Phillies honored him on the outfield wall of Veterans Stadium with his name and a block letter "P" where a retired uniform number would go. The Phillies began using numbers in 1932, and in that season and 1933, Klein wore number 3. He was then traded to the Chicago Cubs, and when he returned to the Phils in 1936, he wore 32 (later retired by the Phillies for Steve Carlton), and soon switched to 36 (later retired by the Phils for Robin Roberts) for that season and 1937. In 1938 he wore number 1 (later retired by the Phils for Richie Ashburn), wore 26 and then 14 (later retired by the Phils for Jim Bunning) in 1939, wore 29 in 1940 and 1941, 3 again in 1942, 8 in 1943 and 26 again in 1944, his last major league season. Rather than choose one of these numbers, the Phils simply retired a "P" for him, as they did for pre-numbers legend Grover Cleveland Alexander).

In 1999, he ranked number 92 on The Sporting News' list of the 100 Greatest Baseball Players, and was a nominee for the Major League Baseball All-Century Team.