The tectonic deformation reaction to multi‐plate convergence in the northern Guizhong Depression, as well as its geodynamic process, remain poorly understood. Two phases of intracontinental deformation are identified using field geological investigations, paleo‐stress inversion and seismic reflection sections: (1) early NE–SW‐directed compression during the Middle Triassic to Early Jurassic; (2) later NW–SE‐directed compression during the Middle Jurassic to Early Cretaceous. The reconstruction of paleo‐stress provides robust constraints on the spatiotemporal evolution of stress within the Guizhong Depression. The regional SW–NE‐directed compression during the Middle Triassic to Early Jurassic was driven by the collision and convergence between the Indochina and South China blocks, resulting in the formation of NW–SE‐directed compressional structures during the Indosinian Period. The later SE–NW‐directed paleo‐stress field was probably driven by the NW‐directed subduction of the Paleo–Pacific Plate during the Middle Jurassic to Early Cretaceous. The Guizhong Depression suffered two periods of compression during the Mesozoic. The early NE–SW‐directed compression was caused by the collision of the Indochina and South China blocks during the Middle Triassic to Early Jurassic, but the later NW–SE‐directed compression was caused by north‐westward flat‐slab subduction of the Paleo–Pacific Plate during the Middle Jurassic to Early Cretaceous.