The primary significance of the Monroe Doctrine in U.S. history was its assertion that the Americas were off-limits to future European colonization or interference, establishing a policy of non-intervention. Introduced by President James Monroe in 1823, this doctrine marked a turning point in U.S. foreign policy, signaling a willingness to assert American influence in the Western Hemisphere. It laid the groundwork for American expansionism and interventionist policies, becoming a cornerstone of U.S. diplomacy in later years.