In this article, we describe a simple and facile approach for the production of ¹²⁵I from the neutron-irradiated natural Xe using wet chemical distillation. First, we outline the design of the irradiation container, its fabrication, cryogenic loading of the gaseous Xe target into the irradiation container, and hermetic sealing of the irradiation container. Qualityassurance tests of the irradiation containers were performed to ensure their safety during neutron irradiation. In light of the implicit need to obtain ¹²⁵I activity with minimum ¹²⁶I radionuclidic contamination, the irradiation time, neutron flux, and target cooling time were judiciously optimized. A thorough optimization of experimental parameters of distillation was carried out to obtain the optimal yield of ¹²⁵I having the desired purity. In each batch, typically 4 g of natural xenon gas was irradiated in the BARC Dhruva reactor for 15 days with a thermal neutron flux of approximately 5 × 10¹³ cm⁻² s⁻¹. After irradiation, the targets were left to decay for typically ∼50 days to reduce the 126I contamination. Several batches of ¹²⁵I were successfully produced using the developed procedure at a level of ∼18.5 GBq (500 mCi) ¹²⁵I per batch. The ¹²⁵I quality in terms of radionuclidic purity, radiochemical purity, and radioactive concentration was evaluated and found to be acceptable for radiolabeling studies. This reported method currently has been adapted for the routine production of ¹²⁵I to meet local needs.