The French traders were the first settlers of Missouri. The ethnic character of the state changed after the Civil War and the the Homestead Act (1862). Germans poured in large numbers in the state followed by Czechs and Italians.  The foreign-born numbered 151,196 in 2000, up from 83,633 in 1990.

Black Americans have witnessed a continuous rise in the population in the recent decades. In 1960 it was 9% which shot up to 10.7% in 1990, and 11.2% in 2000. Kansas City's black community supported a flourishing jazz and urban blues culture between the two world wars. On the other hand St. Louis was the home of Scott Joplin and W. C. Handy in the early years of the century. Of the 629,391 black residents of Missouri in 2000, 178,266 lived in St. Louis, which was 51.2% black. In 2000 Missouri also had 118,592 Hispanics and Latinos. The total Asian population as of 2000 was 61,595.

Only a few American Indians remained in Missouri after 1836. The 2000 census showed an Indian population of 25,076.

The French missionaries brought Roman Catholicism to Missouri in the late 17th century. The first permanent Roman Catholic Church was built about 1755 at St. Genevieve in Missouri. The Catholic population increased with the influx of migrants from Germany, Ireland, Italy, and Eastern Europe during the 19th century. Today, Roman Catholicism remains the largest single denomination. However, the Evangelical Protestants collectively outnumber Catholics. The state's first Methodist church was organized around 1806.

In 2000, Missouri had 856,964 Roman Catholics while Protestants numbered about 797,732. The estimated number of Jews was 62,315 in 2000 and Muslims numbered about 19,359 in the same year.