Caray made his debut in 1945 with the Cardinals, but was fired in 1969 amid rumors of personal problems with the Busch family, who owned both the Cardinals and the Anheuser-Busch breweries. After a season with Oakland, Caray broadcast for the White Sox from 1971 to 1981, and then for the Cubs from 1982 to 1997.
He was extremely popular among the citizens of Chicago and known as much for his public carousing and jovial spirit as his sportscasting. In the years before his death, his skills as a broadcaster gradually declined, due to illness and senility, leading some people to say that he should retire or be fired. His tendency to mispronounce players' names (often humorously), especially late in his career, was widely parodied.
His style became fodder for pop culture parody as well, including a memorable Saturday Night Live recurring sketch featuring Caray (played by Will Ferrell) as a host of a space and astronomy TV talk show.
He was well-known for his exclamation of "Holy Cow!", his "It might be... It could be... It is!" call when a batter hit a home run, and for publicly leading the Wrigley Field crowd in singing "Take Me Out to the Ball Game" during the seventh-inning stretch. He was not a good singer, always singing off-key and with a strained voice, but that was part of the charm of having him sing every game. Since his death, a "guest conductor" has sung the song at each Cubs home game. He had sung the song during the seventh inning for years in the broadcast booth when White Sox owner Bill Veeck secretly amplified his voice for all to hear during one game. The song then became a tradition and possibly his best-remembered trademark.
Although he was known in later years for his deteriorating skills, early in his career, Caray was known for his mastery of all aspects of broadcasting, writing his own copy, conducting news interviews, writing and presenting editorials, and hosting a sports talk program.