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The most crucial issue that affected U.S.-India relations for a long time in the contemporary period is nuclear non-proliferation. Conflicts between the two countries relating to non-proliferation issues had existed for a long period of time. The issue was pitchforked onto the centrestage of world politics with India's Pokharan - II testing in 1998. The United States had assumed leadership role over the non-proliferation regime in recent decades. In attempting to create various regimes to checkmate the proliferation of nuclear weapons and other sensitive technologies, India had been the target of rigorous American approaches on non-proliferation. India, however, has been consistent and vehement in its opposition to various international regimes on the grounds that these are discriminatory and not universal in nature. The present research is an attempt to examine the areas of co-operation and conflict, as far as the nuclear issues are concerned, between the two important democracies of the world, i.e., U.S. and India. It provides a backdrop to the ongoing tussle for power among a nation with the greatest global power and a nation with immense potential power at its disposal.