Chemical short-range order (CSRO), a form of nanoscale special atom arrangement, has been found to significantly alter material properties such as dislocation motion and defect dynamics in various alloys. Here, we use Fe-Ni-Cr alloys to demonstrate how CSRO affects defect properties and radiation behavior, based on extensive molecular dynamics simulations. Statistically significant results are obtained regarding radiation-induced defect propensity, defect clustering, and chemical mixing as a function of dose for three CSRO levels. The perfect random solution as an energetically unfavorable state (negative stacking fault energy) shows the strongest tendency to enable diffusion, while a high CSRO degree scenario generally reduces the effective defect diffusivity due to trapping effects, leading to distinct defect dynamics. Notably, in the high-CSRO scenario, interstitial clusters are Cr-rich and interstitial loops preferentially reside in/near the Cr-rich CSRO domains. It is also identified that CSRO is dynamically evolving in a decreasing or increasing manner upon continuous irradiation, reaching a steady-state value. These new understandings suggest the importance of incorporating the effect of CSRO in investigating radiation-driven microstructural evolution.