This study aims to understand how regional powers construct and maintain their autonomies in the sphere of interest under the great power competition in the region. Although, after the Cold War, the international system has evolved to a uni-multipolar structure, it is still dominated by great powers. Regional powers have been threatened and controlled implicitly or explicitly by them. They establish regional multilateral institutions to decrease great powers’ influence while increasing cooperation in maintaining regional autonomy. In this study, as the consensual hegemon of South America, Brazil’s foreign policy towards the region is analyzed, and how the US, the historically dominant, and China, the new great power, impact Brazil’s autonomy is questioned. During the power transition from the US to China, Brazil found room for manoeuvre for its leadership. Brazil’s changing autonomy between 2000-2018 (with a specific focus on after 2008) is examined using the process-tracing technique in a qualitative case study analysis. The impact of great powers on Brazil’s autonomy during this period is analyzed through interviews with foreign policymakers. As an illustrative case, understanding changing Brazil’s regional autonomy under the shadow of US-China relations will guide us in other regional powers’ interactions with great powers regarding regional politics.