The low-permeability characteristic of sandstone-type uranium deposits has become the key geological bottleneck during the in-situ leaching mining, seriously restricting the development and utilization of uranium resources in China. At present, the blasting-enhanced permeability (BEP) and acidizing-enhanced permeability (AEP) are confirmed to be mainstream approaches to enhance the reservoir permeability of low-permeability sandstone-type uranium deposit (LPSUD). To clarify the synergistic effect of BEP and AEP, the acid-rock reaction and dynamic impact experiments were conducted, aiming to study the effect of chemical reactions on pore structure, dynamic mechanical properties and failure pattern of sandstone. Results show that with the increasing acid-rock reaction time, the total pore volume of samples is promoted largely and exhibits obvious chemical damage. The change of pore volume depends on the pore size, the 100–1000 nm and 1000–10000 nm pores are more susceptible to acid-rock reactions. The dynamic peak strength and the dynamic elastic modulus are decreased and the dynamic peak strain and strain rate are increased when lengthening the acid-rock reaction time, whose evolution laws can be fitted by the logistic expression, the linear expression and the exponential expression, respectively. The acid-rock reactions also have an influence on the fracture development of samples after the dynamic impact. The damaged fractures on the end faces of samples grow from the isolated short fracture, the isolated long fracture to the fracture network, and the damaged fractures on the sides of samples develop from the non-penetration fractures, penetration fractures to the multi-branch fractures. This study clarifies the physical and chemical combined damage mechanism, demonstrates the potential of reservoir stimulation by uniting the BEP and the AEP, and provides a theoretical reference for the reservoir stimulation of LPSUD.