Medwick was born to Hungarian immigrants and grew up in Carteret, New Jersey where his portrait is displayed in Borough Hall rendered by fine art artist Lori Baratta. He made his debut with the Cardinals in 1932. Fans nicknamed him "Ducky Wucky", or just "Ducky", because of his waddle when he walked; but his build led to the nickname of "Muscles" which meant that none of his teammates dared to use the name "Ducky" to his face. His hard-charging style of play got him pulled out of the seventh game of the 1934 World Series by Commissioner Kenesaw Mountain Landis, when Detroit Tigers fans started pelting him with garbage after he slid hard into third base on a triple. (Audio) Landis also ordered Tigers third baseman Marv Owen, into whom Medwick had slid, benched. Medwick remains the only known player to be thrown out of a game for his own personal safety. When asked about the incident by reporters after the game, a perplexed Medwick said, "Well, I knew why [the Tiger fans] threw that garbage at me. What I don't understand is why they brought it to the park in the first place."
A ten-time All-Star, he played for seventeen seasons, finishing with a lifetime .324 batting average. He won the National League Triple Crown and the NL Most Valuable Player in 1937, remaining the last National League player to win a triple crown. Medwick holds the major league record for consecutive seasons with 40 or more doubles, set from 1933 through 1939.
Medwick helped lead the Dodgers to a pennant in 1941, but had lost much of his dominance after being nearly killed by a beanball thrown at him by former Cardinal teammate Bob Bowman, six days after his 1940 trade. In 1946, he was signed as a free agent by the St. Louis Browns. However, after attending 1946 spring training with the Browns, he was not able to secure a spot on the regular-season roster and was seemingly out of baseball at age 34. He eventually returned to St. Louis to finish his career with the Cardinals in 1947 and 1948. He continued playing minor-league baseball through 1952.
During a USO tour by a number of players in 1944, Medwick was among several individuals given an audience by Pope Pius XII. Upon being asked by the Pope what his vocation was, Medwick replied, "Your Holiness, I'm Joe Medwick. I, too, used to be a Cardinal."
Medwick was one of three players born in New Jersey to be elected to the Hall of Fame, and one of five to have attended school in the state—in each case, the only one from the central part of the state. At number 79, he was the highest-ranking New Jersey native to have made The Sporting News list of Baseball's Greatest Players in 1999. That same year, he was nominated as a finalist for the Major League Baseball All-Century Team. He was elected New Jersey athlete of the century at century's end.