Hybrid micro-machining, which integrates several micro-manufacturing processes on one platform, has emerged as a solution to utilize the so-called “1 + 1 = 3” effect to tackle the manufacturing challenges for high value-added 3D micro-products. Hybrid micro-machines tend to integrate multiple functional modules from different vendors for the best value and performance. However, the lack of plug-and-play solutions leads to tremendous difficulty in system integration. This paper proposes a novel three-layer control architecture for the first time for the system integration of hybrid micro-machines. The interaction of hardware is encapsulated into software components, while the data flow among different components is standardized. The proposed control architecture enhances the flexibility of the computer numerical control (CNC) system to accommodate a broad range of functional modules. The component design also improves the scalability and maintainability of the whole system. The effectiveness of the proposed control architecture has been successfully verified through the integration of a six-axis hybrid micro-machine. Thus, it provides invaluable guidelines for the development of next-generation CNC systems for hybrid micro-machines.