Post-Cold War regional security order in Asia is in flux. Growing political, economic and military power of China and India are pressuring existing alliances and power configuration in the region. The dilemma is accentuated by the US attempts to sustain its global leadership role in general, and its influence in the Asian region in particular. India is now recognized as a nascent major power and a ‘natural partner’ of the US, one that many analysts view as a potential counterweight to China’s growing power. Washington and New Delhi have, since 2004, been pursuing a ‘strategic partnership’ based on apparently converging geo-political interests. Numerous economic, security and global initiatives including the plan for ‘full civilian nuclear energy cooperation,’ are underway. Also in 2005, the US and India signed a ten-year defense framework agreement that calls for expanding bilateral security cooperation. Of late, this agreement has been renewed. Given India’s geo-strategic importance and rising political and military clout, these initiatives have the potential to transform India into a major world power. In the wake of China’s growing power and rise as potential challenger to the US primacy in the region, a stronger Indo-US strategic partnership is consequential for security and politics of the region and the world at large. The ongoing power shift from the West to East vis-à-vis contending states’ attempts to assert their influence would have far reaching impact on the regional security order. Therefore, this study examines the dynamics of Indo-US strategic partnership vis-à-vis great power politics and assesses the future security structure of the region. The study also endeavors to develop an understanding on the evolving regional security framework and attempts to explore the nature of Indo-US strategic partnership. In this backdrop, the study also focuses on China’s rise as potential challenger to the US primacy and the US efforts to reinforce existing alliances and build new partnerships with regional countries, which many analysts see as an attempt to manage China’s growing power.