Foxx was born in Sudlersville, Maryland, on October 22, 1907, to Dell and Mattie Foxx, who were farmers. Dell Foxx had played baseball for a town team when he was younger. Jimmie Foxx did well in school but excelled in sports, particularly soccer, track, and baseball. He played all three sports at Sudlersville High School.

After Foxx graduated from the high school. He attended the University of Maryland. He joined a minor league team managed by former Philadelphia Athletics great Frank “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 May 1925 at age 17. He was still in his junior year of high school at the time.

The A’s catching duties were already filled by future Baseball Hall of Fame member 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 a breakthrough year, batting .354 and hitting 33 home runs. That year, Foxx appeared on the cover of Time.

In 1932, Foxx hit .364, with 58 home runs with 169 RBIs, missing the Triple Crown by just three points in batting average. Foxx actually hit 60 home runs that year, which would have tied Babe Ruth’s record, but two of the home runs were hit in games that ended up being rained out, so the home runs did not count. Boston Red Sox first baseman Dale Alexander hit .367, but in just 454 plate appearances; he would not have won the batting title under current rules, which are based upon 3.1 plate appearances per team games played. Foxx did win the Triple Crown the following season, with a batting average of .356, 163 RBIs, and 48 home runs. He won back-to-back MVP honors in 1932 and 1933.

In 1937, Foxx hit a ball into the third deck of the left-field stands at Yankee Stadium, a very rare feat because of the distance and 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.”

On June 16, 1938, he set an American League record when he walked six times in a game. In 1939 he hit .360, his second-best all-time season batting average. His 50 home runs would remain the single-season record for the Red Sox until David Ortiz hit 54 in 2006.

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, filling in at first and third, pinch hitting, and pitching nine games, including two as the starting pitcher. He compiled a 1–0 record and 1.59 ERA over 22⁄3 innings. Foxx was often called the right-handed Babe Ruth, but his career was the opposite of Ruth in this regard. Ruth began his big-league career as a pitcher; Foxx ended his big-league career as one.

Foxx 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 for one season in 1952. He took them to the playoffs where they lost in the first round 2 games to 1 against the Rockford Peaches. Foxx did not return for the 1953 season. From this venture in Foxx’s retirement, the character of Jimmy Dugan, played by Tom Hanks in the 1992 movie A League of Their Own, is loosely based on Foxx, though his players remember Foxx as having behaved significantly more gentlemanly to them than his corresponding character is portrayed in the movie.

Foxx served as head coach for the University of Miami baseball team for two seasons, going 9–8 in 1956 and 11–12 in 1957.

Foxx died in 1967 at age 59 in Miami, Florida. He became ill while eating dinner with his brother and was taken to a hospital, where resuscitative efforts failed. An autopsy showed that Foxx had choked on a piece of food. The year before, Foxx’s second wife, Dorothy, had also died of choking. Foxx is buried at Flagler Memorial Park in Miami.

A statue of Foxx was erected in his hometown of Sudlersville, Maryland, 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.

Foxx finished his 20-year career with 534 home runs, 1,922 runs batted in, 1,751 runs scored, 2,646 hits, 458 doubles, 125 triples, 1,452 bases on balls and a .325 batting average. His 12 consecutive seasons with 30 or more home runs was a major league record until it was broken by Barry Bonds in 2004. 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. He retained these positions until Willie Mays passed Foxx for second place in 1966. Foxx was elected to the Baseball Hall of Fame in 1951.

When the Great Depression fully hit in the early 1930s, A’s owner Connie Mack was unable to pay the salaries of his highly paid stars, and was obliged to sell off a number of them. After a 1936 contract dispute, Mack sold Foxx’s contract to the Red Sox for $150,000 (equivalent to approximately $2,763,669 in 2019 dollars).