Born in Texarkana, Texas, Eddie Mathews was six years old when his family moved to Santa Barbara, California where he developed into a star high school player. Signed by the Boston Braves in 1949, he continued to shine in their farm system as a left-handed power-hitting third baseman who hit towering home runs. Brought up to the major leagues, in his 1952 rookie season with the Braves, Eddie Mathews hit 25 home runs, including three in one game, breaking the record for rookies. In his second year the franchise moved to Milwaukee, Wisconsin where he batted for a .302 season average, hit 47 home runs, and drove in 135 runs. For nine straight seasons he hit 30 home runs or more including leading the National League twice. As one of 1954's superstars in American sports, Eddie Mathews was chosen for the cover of the first-ever issue of Sports Illustrated magazine.

His team won the 1957 National League championship then, helped by Mathews game-winning home run in the tenth inning of game four, they defeated the New York Yankees to win the World Series.

In 1967, Eddie Mathews became only the seventh player to hit 500 career home runs, and is a member of the 500 home run club. When he retired he was seventh in all-time home runs. Over his seventeen-year major league career, he was named to the All-Star team nine times, hit 512 home runs, played in three World Series, and drove in 100 or more runs five times. As the one-two punch for the Milwaukee Braves, from 1954 to 1966 he and teammate Hank Aaron hit 863 homers (Aaron 442, Mathews 421), moving ahead of the duo of Babe Ruth and Lou Gehrig of the Yankees as the all-time leaders in major league history.

Hall of Famer Ty Cobb once said of Mathews: "I've only known three or four perfect swings in my time. This lad has one of them."

In 1978 Eddie Mathews was elected to the Baseball Hall of Fame and today still ranks second all-time among third basemen in home runs, RBI, slugging percentage and total bases. He is the only man to play for the Braves team in all three cities they called home: Boston, Milwaukee and Atlanta. Mathews retired as a player after the 1968 season with final appearances in two post-season games for the World Series champion Detroit Tigers but came back to manage the Atlanta Braves from 1972 to 1974. He was the manager when Hank Aaron hit his 715th home run.

In 1999, he ranked Number 63 on The Sporting News' list of the 100 Greatest Baseball Players, and was nominated as a finalist for the Major League Baseball All-Century Team.

In poor health during his final years, Mathews died from complications of pneumonia at age 69 in La Jolla, California.