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.

The D-Day invasion was designed to retake much of Northern France from German forces in 1944. The intention was to get Allied forces into enemy territory and begin the push towards Berlin. It was led by and organized by American General (and future President) Dwight D. Eisenhower.

The War Production Board was instituted in 1942. Many of the Depression Era government programs were replaced or altered to redirect the focus towards producing weapons and supplies. It led to almost universal employment in the United States as the whole nation was involved in the war effort. It also allowed the United States to produce almost 40% of the entire world's supply of munitions, which outpaced the production of the axis powers (30% of the world collectively). 

In general, workers in the United States benefitted from World War Two. Employment was almost universal and wages and benefits were higher, not to mention the rapid growth of the middle class that took place in the decades after the war. But, one notable negative resulted from the emphasis on the war effort. The government passed a bill to block strikes in essential industries. So those workers who were mining coal or drilling for oil etc. were prevented from striking by force and law. 

Rosie the Riveter was an American propaganda figure and symbol of the contribution of women to the war effort during World War Two. She is a cultural icon meant to stand for the millions of women who worked in munitions factories and worked other jobs traditionally held by men. 

After the Japanese attack on Pearl Harbor, the United States promptly declared war on Japan, and soon after on the other Axis powers. Japanese residents of the United States were viewed with immense distrust and often outright hostility. The government instituted a policy of forced internment in internment camps.

Roosevelt delivered his famous Quarantine Speech in 1937, amidst a climate of isolationism and neutrality in the United States. The majority of Americans did not want to get involved in the budding conflicts of Europe and Asia, but Roosevelt felt differently. In his Quarantine Speech, he argues that the aggressor nations (referring to Italy, Germany, and Japan) should be cut off from international trade and support.