After failing to become a professional baseball player out of high school, Caray sold gym equipment before turning his eye to broadcasting. In 1943 he got his first job calling minor league games for a radio station in Joliet, Ill. He moved on to Kalamazoo, Mich., where he started using his famous home run call, “It might be...it could be...it is! A home run!” Caray started his major league broadcasting career in 1945 with the St. Louis Cardinals. After working for 25 years with the Cardinals, he had a brief one-year stint with the Oakland Athletics in 1970 before moving to Chicago, where he broadcast for the Chicago White Sox for 11 seasons and then with the Chicago Cubs from 1982 until 1997. Caray broadcast more than 8,300 baseball games in his 53-year career.

Wearing oversized thick-rimmed eyeglasses and using the expression “Holy cow” to begin his description of on-the-field plays that caught his attention, Caray became extremely popular throughout the United States. At the Cubs home park, Wrigley Field, he led the fans in singing "Take Me Out to the Ballgame" during the seventh-inning stretch. This tradition was actually started in 1976 during Caray's tenure with the White Sox. His unique style included unintentionally mispronouncing players' names, making outrageous comments that were often unrelated to the action on the field, and being both an outspoken critic and an unabashed fan of the home team. In 1989 Caray was presented with the Ford C. Frick Award and was enshrined in the broadcasters wing of the Baseball Hall of Fame in Cooperstown, N.Y. Both Caray's son Skip and his grandson Chip followed in his footsteps as baseball play-by-play announcers.