No President since Lincoln pursued a more active foreign agenda than Benjamin Harrison. Historians have long debated the extent of Harrison's foreign policy role in comparison to the influence of his secretary of state, James G. Blaine, traditionally seeing Harrison as following Blaine's lead. Recent scholarship, however, credits Harrison with being the driving force in his presidency, especially noting Harrison's growing estrangement from Blaine by 1890.

Harrison achieved remarkable success in several areas. He convened the first modern Pan-American Conference in October 1889 and also boldly negotiated the establishment of a protectorate over the Samoan Islands with Germany and Great Britain. In this post-Reconstruction period, Harrison appointed the nation's leading black leader, Frederick Douglass, minister to Haiti.

On several occasions, Harrison demonstrated that he was willing to go up against foreign nations when American interests were at stake. For example, he took the nation to the brink of war with Chile over an incident involving harm done to United States sailors in Valparaiso. In the end, Chile apologized and paid $75,000 in reparations. The President also confronted an ugly incident with Italy over the mob execution of eleven Sicilian immigrants in New Orleans. Additionally, Harrison stood firm against Britain and Canada to protect the overharvesting of seals in the Bering Sea. As a sign of his interest in defending the nation against foreign powers, Harrison supported the expansion of the Navy, begun by President Chester Arthur, into a world-class fleet of seven armored ships.

President Harrison did not always succeed in pushing forward his foreign policy agenda. For example, he failed to secure a coaling station in Haiti. Likewise, the President could not convince Congress to guarantee the bonds of a private company trying to build a canal in Nicaragua, nor did he achieve the annexation of Hawaii. Harrison strongly advocated the latter issue by sending 150 Marines to protect a white settler government that overthrew Queen Liliuokalani. The Senate, however, refused to consent to a treaty of annexation offered by the Hawaii settlers.

In weighing Harrison's achievements and shortcomings in the area of foreign affairs, there can be no doubt that his administration launched the nation on the road to empire. His firm and purposeful actions, especially in the Chilean and Samoan episodes, inspired Theodore Roosevelt's "Big Stick" diplomacy. Perhaps most importantly, Harrison undertook a vigorous trade agenda, negotiating substantial reciprocal trade agreements with key American trading markets—novel actions that set the pattern for American trade policy in the twentieth century.