FDR's early foreign policy decisions were based largely on what he believed to be in America's best interests. The United States and sixty-five other nations, in the wake of the worldwide Depression, sent delegates to the London Economic Conference in the summer of 1933. Roosevelt had seemed committed to the goals of the conference–to stabilize national currencies on a worldwide front. But Roosevelt had not openly agreed to any of the avowed goals of the conference. When it came to deciding between the gold juggling policies of the first months of the New Deal that seemed to be beneficial for the country or a policy that would have ambiguous short-term effects at home, he chose against worldwide gain and for America alone. His actions angered the rest of the delegates, who called a recess in the conference–a recess that eventually became an adjournment. The world returned to suffering in isolation, a trend that would encourage the rise of the dictators whose ambitions created the Second World War.

Roosevelt's early foreign policy included the unprecedented step of recognizing the Soviet Union in late 1933. He realized that America's refusal to recognize the Bolshevik government, which had been in place for sixteen years at the time, was unrealistic. He realized too that the Japanese and the Germans were both land-hungry and on the rise, and that promoting trade and friendship with the Soviet Union would put the United States at the head of an impenetrable partnership of world powers. Large-scale trade with the Soviet Union, however, never commenced as Roosevelt predicted. But when time came in World War II for America and the Soviet Union to work together, the relationship that Roosevelt had established between the nations allowed him to greet Stalin on a friendly footing.

In addition, Roosevelt had thus far followed a Good Neighbor policy with the countries of Latin America. Whereas Teddy Roosevelt had created an interventionist state with his corollary to the Monroe Doctrine, FDR formally accepted nonintervention in 1933. Roosevelt realized that with dictatorships looming in Europe and the Far East, a Good Neighbor policy might be useful in the West to create a hemisphere-wide defense against looming aggressors. The Good Neighbor policy, which FDR strictly followed in his dealings with Cuba, Haiti, Panama, and the rest of Latin America, was cemented by the trade policy of Secretary of State Cordell Hull. Congress passed the Reciprocal Trade Agreements Act in 1934, which tried to increase export trade and decrease tariffs into the United States. Secretary Hull negotiated twenty-one trade agreements by 1939, and foreign trade with Latin America consequently increased appreciably.

It was into this era of friendly policies and decreased aggression that the governments of Germany, Italy and Japan intervened. But as Hitler and Mussolini cemented their relationship in the Rome-Berlin axis, and Japan stepped up its production of giant battleships in 1934, American isolationism reared its head. Americans, reluctant to repeat the horrors of the First World War, watched wars brewing across seas that seemingly guaranteed continued peace at home. The crisis abroad became more acute when Italy invaded Ethiopia in a bloody quest for more land, but Congress, responding to the mood of an isolationist citizen body, continued to pass Neutrality Acts in 1935, 1936, and 1937. In hindsight, Roosevelt's reluctance to look outside of America and aid its friends in Europe made the job of the dictators much easier. For example, Roosevelt's "gentlemanly behavior" in the Spanish Civil War of 1936–1939, allowing neither the Loyalist regime nor the fascists under Franco to buy much- needed munitions from the United States, speeded the fall of a fellow democracy to fascism. However, American intervention against Franco in Spain would likely have cost the Democrats much of the Catholic vote in the next election–a political sacrifice that Roosevelt would never make.

This isolationist mood of the country was a large reason why Roosevelt failed to involve the United States in World War II in a timely manner. Roosevelt's experience as Assistant Secretary of the Navy had proven his interventionist beliefs correct once, and his actions in the beginning of WWII reveal a similar sentiment in him then. In July of 1937, Japan invaded China, but the lack of a formal declaration of war allowed FDR to continue arms sales to China despite Neutrality legislation. He delivered a speech in Chicago in the autumn of 1937–the "Quarantine Speech"–that called for "positive endeavors" against the aggressions of Italy and Japan, something along the lines of economic embargoes. But faced with an uproar of isolationist protest, the ever politically conscious Roosevelt backed down from his interventionist beliefs. Roosevelt had watched Wilson try and fail to convince the country to join the League of Nations, and had taken to heart the lesson that effective foreign policy abroad required a consensus at home. He thus did not try to change the country's mind. As Clare Booth Luce wrote, "every great leader had his typical gesture; Hitler, the upraised arm, Churchill, the V sign, and Roosevelt?" She wet her finger and held it in the air.

Roosevelt's please-all attitude faced some hurdles when it came to foreign policy. When he finally began American military buildup, he justified himself in press conferences and Fireside Chats using a contradictory mix of isolationist and interventionist reasoning. FDR had his own sources for foreign information, and, as he did with his domestic advisers, he often pitted his foreign policy advisers against each other while keeping control tightly in his own hands. Some historians surmise that Roosevelt encouraged the bad blood between Secretary of State Cordell Hull and his Under Secretary, Sumner Welles, in order to divide the State Department and keep control of it for himself.

As Britain and France finally declared war on Germany and Italy over the invasion of Poland, Roosevelt continued to push for American aid to Britain while trying to keep the country out of war. In this precarious time, he kept mum on the subject of whether or not he would run for a third term, to keep him from entering the lame-duck period of his second term in office. In addition to wanting to keep power in his hands while the country was facing the imminent threat of war, Roosevelt had yet to find a liberal candidate for the Presidency who satisfied him and whom he could groom as a successor.

On April 9, 1940, the Germans overran Denmark and assaulted Norway without formally declaring war. Defeating these countries quickly, the Germans made their way towards Paris. The real threat of Nazi triumph chilled isolationist fervor all over the nation. Roosevelt took this opportunity to push legislation through Congress that would further fortify the American military. On June 10, the President, upon hearing that the French Army had collapsed to the German and Italian army, delivered a momentous speech at the University of Virginia's Commencement exercises. The speech marked a turning point in his attitude to the nation and to the war. It revealed his commitment to everything but war, including unrestricted material aid to the Allies.

Roosevelt also decided to run for a third term, believing that the country needed leadership continuity to face what might become its second great crisis in less than three decades. His decision to run was greeted with a mixture of delight and consternation in Washington because of his momentous break with Washington's two-term tradition. For fear of seeming to force the nomination, FDR did not appear at the Chicago nomination, but was nominated to loud cheers (that he orchestrated with his political cohorts) nevertheless. However, Roosevelt's choice of a running mate, Henry Wallace, a radical and a mystic, was not supported. His Republican opposition was Wendell Wilkie, a successful business tycoon who was a recent convert to the Republican Party. Wilkie had voted for Roosevelt in the election of 1932, but criticized the New Deal and switched parties because of the program's high levels of government intervention.

Wilkie was decried as the rich man's Roosevelt. Indeed, Norman Thomas, the perennial Socialist candidate for President, said of him, "He agreed with Mr. Roosevelt's entire program of social reform and said it is leading to disaster." In his speeches Wilkie represented Roosevelt as a warmonger, although privately he too was a strong supporter of aid to Britain. However, even FDR ultimately caved to the pressure of gaining the worried mothers' vote. He promised in his campaign, "your boys are not going to be sent into any foreign wars. They are going into training to form a force so strong that by its very existence, it will keep the threat of war away from our shores." Wilkie's charges that the New Deal had failed to end unemployment were proven unfounded, as the burgeoning munitions industries slowly absorbed increased numbers of workers–a prelude to the end of the Depression that the war would bring. Roosevelt again prevailed overwhelmingly in the election, defeating Wilkie 449–82 in the electoral college.