Chiozza was born on Tuesday, May 11, 1910, in Tallulah, Louisiana. As a youngster, Lou's family moved to Memphis, Tennessee where he developed into an all-around athlete engaging in basketball, boxing, track, football and handball, as well as baseball. As a multi-sport star in High School, Lou suffered a serious knee injury playing football and this injury almost ended his career, yet he came back from that injury to become one of the fastest men in professional baseball. Chiozza retired from the other sports when he signed to play shortstop for the Memphis Chicks in 1931.
Lou was 23 years old when he was drafted by the Philadelphia Phillies at the close of the 1933 season, and alternated between the infield and outfield for them until the close of the 1936 season. In 1935, Lou's brother, Dino Chiozza was also drafted by the Phillies and they were one of the first sets of brothers to play on the same team in major league baseball. Another brother, Joe, also played professional baseball but didn't make it out of the minor leagues.
While playing for the Phillies, Chiozza was the first major league player in history to bat in a major league night game. He was the leadoff man for the Phillies when he appeared against the Reds in Cincinnati in the first night game in the majors on May 24, 1935. In attendance at the game was Ford Frick, president of the National League. In the White House, president Franklin D. Roosevelt pressed a button that lit up Crosley Field, where a crowd of 20,422 fans, sizable for a last-place team in the middle of the Great Depression, came out to watch the game. Also in 1935, Lou Chiozza tied an NL record with 11 assists in a 9–1 win over Boston.
On May 29, 1935, the Phillies were playing against the Boston Braves at Baker Bowl, the old cracker-box park of the old Philadelphia Nationals. Babe Ruth, playing left field at age 40 for the Braves, had been through for years but was still being exploited for his name. Just a few days before the Philadelphia series, the Babe hit three home runs in Pittsburgh. Chiozza, who had just been brought up from the Memphis Chicks, hit a short fly ball down the left field line that would have ordinarily at best been a double. Due to his advanced age and decreased mobility, Ruth stumbled after the ball in the outfield. The shortstop ran out, retrieved the ball and threw the ball home to barely stop Chiozza from an inside-the-park home run. Many in the park believed that the umpire felt sorry for the aging star and called an obviously safe Chiozza out at home plate. After Ruth realized that he was so slow that Lou almost made a home run on an ordinary base hit, he stood for a minute, folded his glove and walked off the field into the clubhouse. The Babe knew he was done and he officially retired a few days later on June 2, 1935. Chiozza recalled in his later life that he had wished Ruth had retired on a high note after hitting the three home runs in Pittsburgh rather than waiting to play the next series in Philadelphia.
On December 8, 1936, Lou was sold to the New York Giants, for George Scharein and cash, and was then used as a utility infielder and outfielder by the Giants. He played second, third and the outfield with the Giants through the 1939 season. Towards the end of the 1939 season, Chiozza collided with outfielder Jo-Jo Moore while chasing a pop-up hit by St. Louis Cardinals Jim Brown, and this resulted in a compound leg fracture that ended his season. Lou attempted his return in 1940, but he was not able to return to his pre-injury level of play and then retired from the game. He had a lifetime batting average of .277, with .304 in his rookie year the best mark of his career.
Following his retirement from baseball, Chiozza moved back to Memphis where he worked as a local liquor dealer and grocery store owner. He married the former Catherine Lucchesi and had five children, Ann Marie, Lou, Rena, Toni and Libby. Chiozza died on February 28, 1971 and is buried at Calvary Cemetery in Memphis.