The study provides an understandable account of the phenomenon of anti-Americanism that widely prevailed in Pakistan and it became further intense after the start of 21st century. The US drone attacks on Pakistani territory, the Abbottabad operation of the US against OBL and the US attack on Pakistani military post ‘Salala’ remain the leading causes of anti-Americanism in Pakistan. The research identifies that regional policies of United States have created a new dimension of the discourse of anti-Americanism in Pakistan and this phenomenon has brought negative impact on Pak-US relations. The super power’s interests in the region are seen with more clarity by using the lens of realist approach. The Neorealist school of thought comprehensibly covers the international political structure and element of anti-Americanism at global and domestic level. The Neoclassical realism explains the influence of the elite class on policy making and domestic structure of the politics. The theories of Superpower Syndrome and the Dilemma of the Superior observe an image problem of the superpower and also identify an element of jealousy against the superpower. The agenda setting role of Pakistan media analyzes the various dimensions of anti-Americanism in Pakistan. The study explains the multiple causes and the impact of anti-Americanism at global, regional and domestic level. The research at length explains the causes and the impact of the discourse that have significance in the Muslim world, particularly in Pakistan. The Pakistani media identify the media perceptions in highlighting the nature of the Pak-US relations and the element of anti-Americanism. The content analyses of the selected media reveals that content were significantly unfavorable for the US image. The survey also provides the result that depicted the new dimensions of anti-Americanism and its impact on Pak-US relations. The study also provides the viable recommendations for better Pak-US relations in future.