This article analyzes the Tigray crisis in Ethiopia based on the policies of global and regional powers in the context of the African neo-colonial order. The study emphasizes that although the colonial system has ended in the international system, the power struggle in Africa continues through neo-colonialism. The article proceeds with the argument that changing the policies of global and regional actors may result in neo-colonial struggle and instability in Ethiopia. The study aims to define a variable of the approaches of global and regional actors, which is the cause of the instability and neo-colonial struggle experienced due to the crisis in Ethiopia. In this context, the study’s most probable case study method was used and it assumed that the indirect involvement of global and regional actors in the Ethiopian-Tigray conflict has a neo-colonial purpose. Global actors have different interests in line with the regional power struggle and competition. It shows the existence of neo-colonialism as global and regional actors influence Ethiopia’s economic and political systems. Ethiopia’s exposure to neo-colonial interventions hinders these countries’ economic growth and their political, social, and technological development. As a result, it has reached that the neo-colonial struggle has a destabilizing effect on Ethiopia.