In 1866 St Paul High School was  opened in response to requests by students. The oldest continuing high school in Minnesota started with 2 teachers and 12 students in 3 rooms on the 3rd floor of a fish market and dry goods building at 10th and Broadway. J W Foster was the first principal.

In 1883, 223 students moved into the first real school building at 10th and Minnesota. It had 29 rooms. The name was changed to St Paul Central High School in 1888.

Athletics at the school began with a baseball team in 1885, followed by football in 1886, tennis in 1891 and the Girl's Athletic Association in 1896. Boys and girls basketball and track were added in 1901-02.

Construction of the Collegiate Gothic style building at Marshall and Lexington was completed in 1911. The cornerstone for the new building was laid in April , 1912. The "Minutemen" was chosen as the school mascot and the "C" Club was founded. And, in 1912, the new building's  first graduating class of 174 students heard, as commencement speaker,  William Jennings Bryan.

In 1921, the Times began publication followed by the Cehisean in 1922.

By 1936, Central had a student body of 2,900 and in 1939 had its largest graduating class of 874 students. Also in 1939, the Central football/track stadium was constructed. The stadium was renamed Griffin Stadium in 1988 in honor of James Griffin (class of 1939) who was the first black police captain in St Paul, an athlete and an athletic official.

In 1940, Charles Schulz, creator of the "Peanuts" comic strip, graduated. A very shy student and the youngest in his class, his drawings were rejected by the yearbook staff when he submitted them for publication his senior year.

Between 1902 and 1955 Central produced 11 Rhodes Scholars and, currently, has more than any public high school in the United States.