Abstract: Karst damage is a key internal trigger controlling the instability of limestone slopes. To deeply reveal the mechanical response characteristics and failure mechanism of limestone containing cavities, this study adopted multi-scale research methods including uniaxial compression tests, PFC^3D discrete element simulations, digital image correlation technology, and discrete element numerical inversion. The coupling mechanism of different numbers of circular cavities (1-4) and spatial arrangements (transverse/vertical) on the mechanical properties, degradation laws, and failure modes of limestone was quantitatively analyzed. The results show that the peak strength, elastic modulus, and peak strain of transversely arranged specimens exhibit exponential attenuation characteristics, while vertically arranged specimens show a linear decreasing pattern, with the deterioration effect of transverse arrangement on strength parameters being 37.2% higher than that of vertical arrangement. Single-cavity specimens exhibit typical diagonal shear failure, while multi-cavity specimens (n≥2) evolve into vertical through-going splitting failure. When the number of circular cavities increases from 1 to 4, the crack initiation stress significantly decreases from 166.86 MPa to 154.32 MPa, a reduction of 12.5%. This study establishes a nonlinear attenuation model between the number of circular cavities and peak strength, reveals the strength degradation laws under different arrangements, and verifies the directional control effect of circular cavity spatial configuration on failure modes. The research results provide theoretical basis and technical support for the stability evaluation of engineering rock masses and the prevention of geological disasters in karst areas.