Cermak was born about 50 miles (80 km) from Prague but celebrated his first birthday on Ellis Island in New York Harbor. His parents settled in Braidwood, Illinois, where, as an adolescent, Anton followed his father into the coal mines. In 1890 Cermak moved to Chicago and, after holding a number of minor jobs, established himself successfully in business. Meanwhile, he was also making his mark in the city's Democratic Party organization. He started out as a clerk, advanced to precinct captain, and in 1902 won a seat in the state legislature. He stayed there until 1909, when he became an alderman in the Chicago City Council. After a tenure as bailiff of the municipal court, he returned to the City Council in 1919.

In 1922 Cermak's political career took a major step forward when he was elected chairman of the Cook County Board of Commissioners. By 1928 he was undisputed leader of the local Democratic Party, and his adroit use of patronage and other aspects of the emerging Democratic machine in Chicago brought him the mayoralty in 1931. On the national front, Cermak's influence was decisive in bringing Illinois into the Roosevelt camp at the 1932 Democratic National Convention.

On February 15, 1933, while riding in Roosevelt's open touring car, Cermak was wounded by a gunshot intended for the president-elect; he died three weeks later.