Invasive fish species pose a significant danger to biodiversity and cost the economy billions of dollars by destroying ecosystem of open water fisheries. Currently, management propositions such as use of biocides, physical removal by repeated netting, barriers and lowering water levels to disrupt spawning ground are the only available approaches to control the non-native invasive fishes. Here, we demonstrated an alternative biological method, using common carp (Cyprinus carpio) as experimental model, to eradicate the non-native invasive fish species from large inland open waters. We first depleted the endogenous germ cells of adult C. carpio by combination of cytotoxic drug Busulfan (40mg/kg; total 5 dosages) and elevated water temperature (38°C) treatments within 10 weeks. The efficacy of treatments was evaluated by histological and vasa gene expression studies. Our study revealed that, at the end of 10 weeks treatment period, all the animals (n=5; each sex) turned sterile and remained in that condition post termination of recovery period (animals were reared at water temperature of 25°C for additional 10 weeks). Later, we paired them with the sexually matured wild counterparts in natural spawning trial. We observed that, although sterile male and female actively participated with their wild counterparts during the spawning trial, no progeny were detected in the tank; suggesting a viable approach to eradicate and/or control the non-native invasive fish species in open water bodies.