This study investigates the role of economic sanctions within contemporary national security strategies, focusing on their impact, motivations, and implications for sender states. Utilizing a mixed-methods approach, the research combines qualitative and quantitative methodologies to comprehensively analyze unilateral and autonomous economic sanctions imposed by the U.S. and the EC/EU between 1950 and 2019. The comparative and descriptive analysis examines 97 sanctions episodes, including 60 unilateral U.S. sanctions and an original dataset of 37 EC/EU autonomous economic sanctions episodes. The findings reveal that economic sanctions imposed by both entities generally yield positive economic outcomes for sender states. Endogenous motivations such as economic security concerns, geopolitical interests, and domestic political considerations emerge as significant drivers behind the deployment of sanctions. Economic sanctions are perceived as a strategic tool serving political objectives while enhancing economic security of sender states. Tangible benefits, including strengthened negotiating positions and domestic support, underscore the instrumental role of sanctions in advancing sender states’ interests globally. In summary, this research contributes valuable insights into the complex dynamics of economic sanctions and their implications for sender states. The study offers pertinent guidance for policymakers, scholars, and practitioners navigating global security and economic governance challenges by examining economic sanctions’ motivations, impacts, and implications within contemporary national security strategies.