CO2 flooding in ultra-low permeability reservoirs is an effective means to boost oil production, while the complex fractures formed by fracturing in the initial development stage induce severe CO2 channeling. Therefore, a CO2-responsive coupling system, which coupled CO2-responsive gel particles (CRPGP) with CO2-responsive wormlike micelles (CTWM) was prepared to restrain CO2 breakthrough. To testify the EOR capacity during CO2 flooding of the responsive coupling system, the interaction between CRPGP and CTWM, and responsiveness of coupling system was investigated, followed by core flooding and rock slab flooding experiments. Experiment results showed that after the coupling system was exposed with CO2, the particle size of CRPGP increased, spherical micelles of CTWM transformed to wormlike micelles, CRPGP and CTWM were integrated through hydrophobic association among wormlike micelles and hydrophobic chains in CRPGP, and the coupling system’s apparent viscosity increased from 10.4 mPa·s to 2339 mPa·s. Moreover, 0.5 pore volume (PV) CO2-responsive coupling system injection and further CO2 flooding could dramatically boost oil production in fractured cores and rock slabs, which was primarily ascribed to the aggrandizement of sweeping volume resulting from the plugging effect of CRPGP and mobility ratio improvement of the coupling system. Compared with single slug plugging of fractures, multi-stage regulation of fractures could establish a higher-pressure gradient, and more crude oil in the matrix was activated with enhanced oil recovery (EOR) of 22.8%. All the experimental results demonstrated that the CO2-responsive coupling system has great EOR capacity during CO2 flooding, which provided novel insights for ultra-low permeability reservoirs EOR technology that incorporated with CO2 resource utilization and storage.