Exploring the transformation of spatial mechanisms from their unfolded to controlled folding states to meet the requirements of various application scenarios has long been a hot topic in mechanical structure research. Although conventional spatial mechanisms can be designed to meet almost any application scenario, the design’s complex and excessive combinations of structural components, kinematic pairs, and drive units are unavoidable. It introduces many problems, such as poor reliability, drive complexity, and control difficulties. Based on 4D printing technology, the design of self-folding spatial mechanisms that use pre-stressed response properties under predetermined thermal excitation to achieve different shrinkage ratios integrates the control and drive system and the structural components and kinematic pairs. It brings novel features of self-folding while effectively avoiding many problems associated with conventional mechanical design. Further, the pre-stressed response model introduces the self-folding spatial mechanisms’ excitation, morphing, and driving investigation. Self-folding spatial mechanisms with different shrinkage ratios were prepared via fused deposition modeling, which verified the theoretical analysis and pre-stress response model and the design’s correctness and feasibility by experiments. The existing 4D printing technology lacks a paradigmatic design method in the application field. Contrarily, this work organically combined the conventional mechanical structure design with materials and fabrication via fused deposition modeling. A systematic study of self-folding spatial mechanisms from structural design to morphing control was carried out. This design is expected to introduce a novel paradigm of 4D printing technology in conventional mechanical design and has considerable application prospects in spherical radar calibration mechanisms.