Although Foxx's name appears both as Jimmy Foxx and Jimmie Foxx in newspaper accounts, box scores, baseball cards, and other records, Foxx generally signed his name "Jimmie."

Born in Sudlersville, Maryland, Foxx (nicknamed "Double X" and "The Beast") played baseball in high school and dropped out to join a minor league team managed by former Philadelphia Athletics great "Home Run" Baker. Foxx had hoped to pitch or play third base, but since the team was short on catchers, Foxx moved behind the plate. He immediately drew interest from the Athletics and New York Yankees. Foxx signed with the A's and made his major league debut in 1925 at age 17.

The A's catching duties were already capably filled by future Hall of Famer Mickey Cochrane, so by 1927, Foxx was splitting time between catching, first base, and the outfield. In 1929, installed as the A's regular first baseman, Foxx had his breakthrough year, batting .354 and hitting 33 home runs. In 1932, Foxx hit 58 home runs, which stood as the single-season record for a right-handed batter for 56 years until Mark McGwire hit 70 in 1998. He followed up in 1933 by winning the Triple Crown with a batting average of .356, 163 RBIs, and 48 home runs. He won back-to-back MVP honors in 1932 and 1933.

When the Great Depression hit, A's owner Connie Mack softened the blow to his pocketbook by selling off some of his star players. In 1936, Mack sold Foxx's contract to the Boston Red Sox for $150,000 following a contract dispute.

Foxx played six years in Boston, including a spectacular 1938 season in which he hit 50 home runs, drove in 175 runs, batted .349, won his third MVP award, and narrowly missed winning the Triple Crown. In 1939 he hit .360, his 2nd all-time best annual batting average.

Foxx's skills diminished significantly after 1941. Some sources attribute this to a drinking problem, while others attribute it to a sinus condition. He split the 1942 season between the Red Sox and Chicago Cubs, playing mostly a reserve role. He sat out the 1943 season and appeared only in 15 games in 1944, mostly as a pinch hitter.

He wound up his career with the Philadelphia Phillies in 1945 as a jack of all trades, filling in at first and third, pinch hitting, and even pitching 9 games, compiling a surprising 1-0 record and 1.59 ERA over 22 2/3 innings. Interestingly, the man who was so often called the right-handed Babe Ruth throughout his career was the opposite of Ruth in this regard as well. Ruth began his big-league career as a pitcher; Foxx ended his big-league career as one.

Jimmie Foxx finished his 20-year, 2317-game career with 534 home runs, 1922 runs batted in, and a .325 batting average. He won a total of three MVP awards. His 12 consecutive seasons with 30 or more home runs was a major league record broken by Barry Bonds in 2004. He was inducted into the Baseball Hall of Fame in 1951. At the end of his career, his 534 home runs placed him second only to Ruth on the all-time list, and first among right-handed hitters, positions he retained for some 26 years.

Foxx was one of the most feared sluggers of his era. Lefty Gomez once said, "He (Jimmie Foxx) has muscles in his hair." In 1937, Foxx hit a ball into the upper deck at Yankee Stadium in New York, a very difficult feat due to the distance and to the angle of the stands. Gomez was the pitcher who gave it up, and when asked how far it went, he said, "I don't know, but I do know it took somebody 45 minutes to go up there and get it back."

A series of bad investments left Foxx broke by 1958. He worked as a minor league manager and coach after his playing days ended, including managing the Fort Wayne Daisies of the All-American Girls Professional Baseball League. Tom Hanks' character Jimmy Dugan in the movie A League of Their Own was largely based on Foxx, but the producers took a number of liberties in creating the role.

Foxx died at age 59 in Miami, Florida, apparently by choking to death on a bone. He is buried at Flagler Memorial Park in Miami, Florida. A statue of Foxx was erected in his hometown on October 25, 1997.

In 1999, he ranked number 15 on The Sporting News' list of the 100 Greatest Baseball Players, and was a nominee for the Major League Baseball All-Century Team.