Missouri became the twenty-fourth state with its admission to the Union on 10 August 1821. Its central location, navigable waterways and variable terrain attracted settlers from every part of the country as well as from abroad. Missouri was settled by people from New England, the Ohio Valley, the Appalachian region, and the upper South, as well as from Germany and other European nations.

Four major migrations influenced Missouri's settlement. The first began during the Spanish and French control when each encouraged American settlement due to their fear of British encroachment. A colony came with Colonel George Morgan and settled near New Madrid. This is known as the first distinctly American settlement. In 1797 Moses Austin helped develop a sizeable settlement at Mine a Breton, and in 1798 Daniel Boone was offered 1,000 arpents of land if he would move to Missouri and bring new settlers with him. This group settled in 1798 in what is now the area of St. Charles County. That same year a group of German-Swiss from North Carolina settled near the Whitewater Creek bottoms in present-day Cape Girardeau and Bollinger counties.

The second wave of settlers came with the acquisition of the territory by the United States in 1803. The population of the state grew from 10,000 people in 1804, to over 65,680 by 1821 when the state was admitted to the Union. During this time period, boundaries were changing rapidly, and the researcher will find it necessary to follow these changes in order to locate required records.

The third major wave was between 1820 through 1860 when the Ohio-Mississippi-Missouri river system and the extension of the Cumberland Road to the Mississippi River brought thousands of immigrants from the upper South and lower Midwest into Missouri, pushing the frontier to the Kansas border. Kentucky contributed the largest number of settlers during this period, followed by Tennessee, Virginia, Ohio, Indiana, and Illinois. The mountaineers from middle or east Tennessee and North Carolina were especially attracted to the Ozarks. Many of the Missouri and Mississippi river settlements were established by Southerners who maintained their political sympathies, slavery and Democratic politics. They settled along the Mississippi River well north of St. Louis and across the Missouri Valley. Kentucky contributed a large proportion of settlers to the middle prairie regions, while the people from Ohio, Indiana, and Illinois concentrated along the northern border and the Mississippi River. During this period, Germany also contributed a large number of settlers who settled in St. Louis and along the river counties west.

Much of the land purchased during this period was through the federal land offices located in strategic positions throughout the state. The first land offices were established in 1818 at Jackson, Franklin and St. Louis.

Immigration, for all intents and purposes, came to a stand-still during the Civil War; but with peace, the fourth wave of settlers arrived. With the help of the railroads, Europeans as well as pioneers from the prairie states of Ohio, Indiana, Illinois, and Iowa provided the major portion of newcomers. Northerners outnumbered Southerners nearly two to one. They occupied most of the remaining land north of the Missouri River, along the Kansas border, and along the Osage and Springfield plains. During this period the cities of St. Louis, Kansas City, Joplin, Springfield, and Jefferson City also grew rapidly. By 1890 the population of Missouri had reached 2,679,185.