The League of Nations was an important component of Woodrow Wilson's Fourteen Points and the Treaty of Versailles. It was meant to serve as a sort of proto-United Nations, designed to facilitate freedom of trade and prevent war; however, it was doomed to failure from the very start due, in part, to the efforts of one American senator. Henry Cabot Lodge was the Senate Majority Leader at the time that the Treaty of Versailles appeared before the Senate for ratification. He wanted the treaty amended to ensure that America would remain isolationist and not involved in the League of Nations. His refusal, along with others', to support the League of Nations ensured that the treaty was never ratified in the United States' Senate. 

Although the United States declared war on Germany and the Central Powers in April of 1917, the first members of the American Expeditionary Force did not join the fighting until October of that year. Even then, there were barely tens of thousands of Americans fighting on the Western front, among millions of British, French, and Germans (as well as various citizens of those countries' colonial empires). By the spring of 1918, the number of Americans on the Western front was in the millions, and they decisively turned the tide of the war.

The Selective Service Act of 1917 allowed the Federal government to compel young men between the ages of 21 and 30 to register for draft eligibility. Over two-and-a-half million Americans were drafted under the Selective Service Act.

During World War One, Mexico adopted a position of consistent neutrality. They traded with both the Allied and Central Powers and refused invitations from the Germans to declare war on the United States and vice versa. 

For the most part, Latin America remained wholly neutral throughout World War One. The German policy of unrestricted submarine warfare tested this neutrality, as did Britain's policy of seizing ships bound for the Central Powers. Diplomatic relations were frequently strained, but none of the countries thought it in their best interest to declare war, except for Brazil. Following a series of German attacks on Brazilian merchant ships in 1917, the country declared war on Germany. 

In 1916, the Mexican revolutionary known usually by his nickname, Pancho Villa, led a raid into American territory in New Mexico and Texas, during which American citizens were murdered. He was pursued by the American general, John J. Pershing, and the conflict almost led to a full-scale war between the United States and Mexico. This conflict abated, however, when the United States declared war on the Central Powers and joined World War One.

The Committee on Public Information was led by Chairman George Creel. It was set up in 1917 to encourage public support for the American war effort. This goal was mostly achieved through widespread propaganda campaigns linking the war effort to patriotism and nationalism. 

During the Second World War, people of Japanese ancestry—both citizens of Japan living in America and Japanese-Americans—were sent to camps where they were forcibly interned until the war was over. Even though people of Germans and Italian descent might have been perceived as being the United States' combatants as much as people of Japanese descent, individuals of German or Italian descent were more difficult to identify racially and not interned. In recent years, the United States' internment of people of Japanese descent during World War Two has been widely condemned as unneccesary and a violation of the same rights for which the United States was fighting.

The Neutrality Act of 1939 forbade the United States from involving itself in any conflict between the various European powers; however, seeing the direction the war was turning and the need for American intervention, Roosevelt encouraged the passage of the Lend-Lease Act of 1941, which allowed America to send supplies and money to the allied powers of Britain and the Soviet Union without violating the Neturality Act by actually putting American soldiers on the ground.

The Potsdam Conference was the final meeting of three great world powers (Britain, Russia, and the United States) in the waning moments of World War Two. It occurred shortly after the death of Roosevelt, so the United States was represented by President Harry Truman.