First let me address nilhaus's answer:

Was it politically expedient for the United States to remain neutral even after Hitler rose to power? How about after Hitler invaded France? In any case, the President of the United States Franklin Roosevelt did not think so, as he struggled to convince an isolationist citizenry to support greater measures of support for Great Britain. In fact, Roosevelt had definitively opposed isolationism since 1937, when he gave his famous Quarantine Speech in Chicago (a sort of center for isolationist sentiment) calling for greater international cooperation in containing aggressors, presumably Japan, Italy, and Germany. Reactions among the American population were mixed.

Anyway, to answer the original question (I'm not going to address whether the United States was really isolationist during the 1920s & 1930s, but answer why the nation so clearly emerged as the leader of the Western World when it so clearly shirked from that role prior to its entry into WWII), I'll list some of the most accepted causes within the literature.

1. Franklin Roosevelt, as a self-identified heir of Woodrow Wilson, personally desired for the United States to take a leading role in the West.

2. The concept of the "United Nations" was seen as essential to winning the war and the peace, as Roosevelt and others were fond of saying. They strongly pushed the idea of the United Nations both during and after the war. My thesis adviser recently published a book on this topic, One World, Big Screen, which I would advise you to read if you are interested in the rise of American diplomacy/the use of film as propaganda.

3. The American consciousness came to accept that isolationism had been a cause of Hitler's easy rise to power within Europe (i.e., at Munich) and thus the cause of a war that ultimately drew in the United States anyway.

4. The emerging power of the United States necessitated that it take a greater role in world affairs.

5. Perhaps most importantly, the Second World War ended not just with the rise of American power but also the rise of Soviet power. With one enemy in Europe down, another enemy appeared, and one which threatened to undermine American interests and values throughout Europe and the world. By 1949, this nation had developed its own atom bomb. By the 1950s, it displayed a technological savvy that could drop a payload on any American city at any time. The United States at this point had lost its ability to be isolationist, as the oceans that had protected it from the rest of the world could no longer protect it from the Soviet Union.

This is just a quick summary from a student of the history of American foreign policy (soon to have his Master's). These are the basics, but I think it is what you wanted to know.