In the history of the United States, the period from 1918 through 1945 covers the post-World War I era, the Great Depression, and World War II. After World War I, the U.S. rejected the Treaty of Versailles and did not join the League of Nations. 

In 1920, the manufacture, sale, import and export of alcohol was prohibited by an amendment to the United States Constitution. Possession of liquor, and drinking it, was never illegal. The overall level of alcohol consumption did go down, however, state and local governments avoided aggressive enforcement.  

The Wall Street bombing occurred at 12:01 pm on Thursday, September 16, 1920, in the Financial District of Manhattan, New York City. The blast killed thirty people immediately, and another ten died later of wounds sustained in the blast. There were 143 seriously injured, and the total number of injured was in the hundreds.The bombing was never solved, although investigators and historians believe it was carried out by Galleanists (Italian anarchists), a group responsible for a series of bombings the previous year. The attack was related to postwar social unrest, labor struggles, and anti-capitalist agitation in the United States.

The Wall Street bomb killed more people than the 1910 bombing of the Los Angeles Times, which was the deadliest act of terrorism on U.S. soil up to that point.

Was a time of high economic growth and general prosperity. It was also a time of confrontation as the capitalist United States and its allies politically opposed the Soviet Union and other communist states; the Cold War had begun. African Americans united and organized, and a triumph of the civil rights movement ended Jim Crow segregation in the Southern United States. Further laws were passed that made discrimination illegal and provided federal oversight to guarantee voting rights.

Early in the period, an active foreign policy was pursued to help Western Europe and Asia recover from the devastation of World War II. The Marshall Plan helped Western Europe rebuild from wartime devastation. The main American goal was the Containment of communism. An arms race escalated through increasingly powerful nuclear weapons. The Soviets formed the Warsaw Pact of European satellites to oppose the American-led North Atlantic Treaty Organization (NATO) alliance. The U.S. fought a bloody, inconclusive war in Korea and was escalating the war in Vietnam as the period ended. Fidel Castro took power in Cuba, and when the USSR sent in nuclear missiles to defend it, the Cuban Missile Crisis of 1962 was triggered with the U.S., the most dangerous point of the era.

On the domestic front, after a short transition, the economy grew rapidly, with widespread prosperity, rising wages, and the movement of most of the remaining farmers to the towns and cities. Politically, the era was dominated by liberal Democrats who held together with the New Deal Coalition: Harry Truman (1945–1953), John F. Kennedy (1961–1963) and Lyndon Johnson (1963–1969). Republican Dwight D. Eisenhower (1953–1961) was a moderate who did not attempt to reverse New Deal programs such as regulation of business and support for labor unions; he expanded Social Security and built the interstate highway system. For most of the period, the Democrats controlled Congress; however, they were usually unable to pass as much liberal legislation as they had hoped because of the power of the Conservative Coalition. The Liberal coalition took control of Congress after Kennedy's assassination in 1963, and launched the Great Society.

This period of Post–World War II economic expansion witnessed the rapid growth of suburbs and a growing middle class.

The Vietnam War (also known by other names) was a conflict in Vietnam, Laos, and Cambodia from 1 November 1955 to the fall of Saigon on 30 April 1975. It was the second of the Indochina Wars and was officially fought between North Vietnam and South Vietnam. The north was supported by the Soviet Union, China, and other communist states, while the south was supported by the United States and other anti-communist allies. The war is widely considered to be a Cold War-era proxy war. It lasted almost 20 years, with direct U.S. involvement ending in 1973. The conflict also spilled over into neighboring states, exacerbating the Laotian Civil War and the Cambodian Civil War, which ended with all three countries becoming communist states by 1975.

The history of the United States from 1964 through 1980 includes the climax and end of the Civil Rights Movement; the escalation and ending of the Vietnam War; the drama of a generational revolt with its sexual freedoms and use of drugs; and the continuation of the Cold War, with its Space Race to put a man on the Moon. The economy was prosperous and expanding until the recession of 1969–70, then faltered under new foreign competition and the 1973 oil crisis. American society was polarized by the ultimately futile war and by antiwar and antidraft protests, as well as by the shocking Watergate affair, which revealed corruption and gross misconduct at the highest level of government. By 1980 and the seizure of the American Embassy in Iran, including a failed rescue attempt by U.S. armed forces, there was a growing sense of national malaise.

The period closed with the victory of conservative Republican Ronald Reagan, opening the "Age of Reagan" with a dramatic change in national direction.

The history of the United States from 1980 until 1991 includes the last year of the Jimmy Carter presidency, eight years of the Ronald Reagan administration, and the first three years of the George H. W. Bush presidency, up to the collapse of the Soviet Union. Plagued by the Iran hostage crisis, runaway inflation, and mounting domestic opposition, Carter lost the 1980 United States presidential election to Republican Reagan.