The major conflict that marked a shift in U.S. foreign policy towards interventionism was the Spanish-American War of 1898. This conflict stemmed from U.S. support for Cuban independence and resulted in the defeat of Spain. The aftermath significantly altered U.S. foreign relations, as the nation acquired territories such as Puerto Rico, Guam, and the Philippines. This war not only demonstrated American military power but also facilitated a transition from isolationism to a more assertive global presence, paving the way for subsequent interventions in foreign conflicts.