This paper examines the influence of culture in the field of international relations, and explores the roles that various aspects of culture play in the processes of international communications within the interactions between the United States (US) and the European Union (EU). This paper is the report of a three year case study that investigates the roles cultural influences play in international relations and foreign policy making between the countries of the EU and the US in the years preceding and since the 2003 US-led invasion of Iraq. The main findings from this case study demonstrate that there are greater cultural implications of leadership and on the other hand public perception that create important factors in the processes of international socio-political changes. These factors critically influence the effectiveness of collaborative approaches between the EU and US in terms of international relations and foreign policy making. The cultural aspects examined in this study include: nationalism vs. patriotism, political traditions, security concerns, human rights, the international democratic deficit, language, identity, miscommunication, misperception, diplomacy, mission vs. vision, conflict, and cultural negotiations. The study showed that culture plays a critical role in the construction of different types of communications and interactions in relations between the EU and US. The research also discovered that additional and contemporary cultural studies in this field are needed to systematically define some aspects of culture as politically internal and external active elements of change, especially in terms of multilateral relations.