This study investigates the impact of domestic sewage wastewater irrigation on the cultivation of cassava (Manihot esculenta Crantz) from selected agrofields of Palakkad, Kerala with a comparison of well-water-irrigated M. esculenta from the same area. For this, the physicochemical parameters of respective water and soil samples were analysed. Further, to understand the post-harvest crop quality which includes the peeled tuber, peel, leaf and stem proximate composition, and mineral contents including heavy metal composition and in vitro antioxidant potential. The results of the physicochemical parameters of both domestic sewage wastewater and well-water irrigated samples (both water and soil) were observed within the permissible limits according to the WHO/FAO suggested pattern. Interestingly, heavy metals such as Zn, Cd, Cr, Cu, and Ni were within the admissible limit in respective samples from both fields. In general, when compared with well-water irrigated cassava crop samples, the antioxidant potential was significantly higher (p < 0.05) in sewage wastewater irrigated cassava samples. The present study demonstrated that domestic sewage water was found to have promising physicochemical properties that allow for safe use for irrigation as liquid organic fertilizers and the cassava crop residues from such agrofields could also be exploited as potential animal feed.