After the war, Missouri entered a long period of recovery and readjustment. The Radical Republicans held power briefly, but were displaced by the Democrats, who won the election of 1872 and remained the dominant political force during the last quarter of the 19th century.

When the rivers were the main routes and steamboats the chief mode of transportation, Missouri had close ties with New Orleans and the South. However, as railways were extended and steamboating declined, the state became more closely allied with the North and the East. St. Louis and Kansas City grew into large industrial cities. Many European immigrants were attracted to these new manufacturing centers. Wages remained low, however, and there was widespread industrial unrest, with workers striking to demand reforms. There also was much rural discontent. Although improved farming methods were adopted and production increased, farmers did not become prosperous.

In the early years of the 20th century, the reform administrations of governors Joseph W. Folk (1905–09) and Herbert W. Hadley (1909–13) sponsored many progressive measures. The direct primary, the initiative, and the referendum were enacted. Monopolies were prosecuted. Railroads were placed under stricter controls, and public utilities and child labor were regulated.

The first two decades of the 20th century were prosperous. In the early 1920's, however, farm prices fell drastically, and the state's agriculture was plunged into depression. A decade later, the Great Depression caused widespread economic hardship. During this period, the state set up welfare programs to aid the needy and expanded its public works programs.

World War II brought diversification of industry and a general prosperity. During the war, the first Missourian to become President, Harry S. Truman, took office. In the mid-20th century, the long-depressed Ozark region of the south emerged as a vacation area. The damming of rivers for flood control created large artificial lakes that became recreation centers.

In 1973, many sections of the state were inundated by the waters of the Mississippi and Missouri rivers in the worst floods in Missouri's history. This flooding was surpassed by the Great Flood of 1993, in which 24 persons died, 1.7 million acres (688,000 hectares) were flooded, and damages to property and crops totaled $2.7 billion.

In the 1970's, Missouri's urban populations, primarily in the middle-class, began to move to the suburbs. The larger cities, such as Kansas City and St. Louis, suffered both from loss of financial support as well as inadequate public transportation and rising levels of crime. Downtown redevelopment programs began in an effort to attract tourists and new businesses. Farm equipment production and expanded factories helped the state's economy stay strong through the late 1990's and into the early 2000's. Tourism then became a billion-dollar industry for the state; St. Louis, Kansas City, and Springfield hosted many conventions, while the Ozarks and nearby Branson attracted vacationers.

Environmental problems arose in the early 1980's through the 1990's; runoff, the discovery of toxic chemicals in fish, and groundwater contamination all plagued the Missouri landscape throughout the state. In Times Beach, near St. Louis, poisonous dioxin was found; the U.S. government bought the homes and businesses located there and finished cleanup in 1997. The land was then turned over to the state, and Route 66 State Park was established.