Amid the dual challenges of advancing deep mining operations and achieving carbon peak and neutrality targets, maintaining safe production in underground mines has become a critical imperative for national resource security. Many underground mines in China have adopted large-diameter deep-hole mining as their primary production method, forming chambers with spans exceeding 20 meters under site-specific geological conditions. Given the complex underground conditions and recurring dynamic stresses from production blasting, analyzing the dynamic response of large-span chambers is critical. This study uses the Panlong lead-zinc mine as a case study and applies combined FEM-DEM numerical simulations to investigate how blast distance and chamber span affect the stability of the upper chambers. The results demonstrate that: (1) With a constant chamber span, decreasing blast distance from 27.5 m to 2.5 m increases post-blast plastic zone volume and fracture density by 251.41% and 42.12%, respectively, while repeated blasting significantly undermines chamber stability; (2) Reduced blast distances correspond to 66.25% and 373.37% increases in shear and tension-shear failure blocks per blast, evolving failure patterns, intensified peak particle velocity (PPV), and markedly compromised stability; (3) During cyclic blasting, larger spans induce roof displacement growth from 0.07 cm to 2.08 cm due to caving, alongside 195.35% and 208.49% increases in plastic zone volume and fracture density, respectively, progressively weakening large-span chamber stability; (4) Large-span chambers exhibit unstable conditions with extensive elastic energy accumulation at elevated levels post-excavation, where subsequent blasting disturbances promote further energy storage, substantially raising overall collapse risks. These findings provide valuable insights for underground mining operations regarding blasting design and support engineering.