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.

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.

The Sussex Pledge was issued by the German government in 1916. It was issued in response to a statement made by President Woodrow Wilson that the United States would enter the war if Germany did not stop its policy of unrestricted submarine warfare. The Sussex Pledge promised to stop sinking American ships and to allow partial freedom of the seas; however, the German government rescinded the policy in January of 1917, believing that they could win the war by preventing France and England from trading with the United States. This backfired and caused the United States to join the war on the side of the Allied Powers.

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.

The primary contribution of Brazil during the First World War came from its contribution of raw and luxury resources to the Allied Powers, particularly when this became exclusive following Brazil's declaration of war in 1917; however, the primary military contribution of Brazil was the support its navy to help the efforts of the Allied Powers to pursue German submarines, which allowed for Allied control of the Atlantic Ocean.

At the time of the First World War, the four biggest Latin American economies were Mexico, Chile, Brazil, and Argentina. All four countries were, at least in the cities and coastal regions, relatively modernized, and they all engaged in widespread trade with the rest of the world. Brazil, in particular, had many raw and luxury resources to export and Argentina had a consistent surplus of grain, wheat, and meat products. All four of these nations would play an important role in the First World War, either by remaining neutral and supplying the Allies and the Central Powers with supplies (Mexico, Chile, and Argentina) or by declaring war on Germany and hounding their ships in the Atlantic (Brazil).

The Treaty of Versailles set the terms by which the combatants of World War One would progress in the wake of World War One, and it established very harsh and humiliating conditions for Germany. Germany was forced to pay war reparations and accept full responsibility for the war. By 1924, it had become clear that Germany could not pay off its massive debt, and its attempts to do so were causing hyperinflation. In an attempt to remedy this situation, the Dawes Plan restructured German debt and lent a great deal of money from the U.S. treasury to the German government.

The Zimmerman Telegram was a message from the German high command to the Mexican government, which promised that if Mexico attacked the United States during World War One, then the German government would return Mexican territory in the southwest of the United States in the event of a German victory. The telegram became public knowledge and was one of the main reasons why the United States declared war on Germany in 1917.

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.

The Palmer Raids can be seen in the larger context of the Red Scare that gripped American society after World War One. The Palmer Raids were designed to forcefully exile foreign citizens living in America who were deemed radical leftists; anarchists and communists were particularly likely to be targeted.