There is increasing concern about the toxic effects of chemical pesticides on human health and the environment. Many alternatives, however, are viewed as impracticable or inefficient for agricultural needs. Here, a sustainable, environmentally friendly strategy was designed for the control of major rice insect pests (i.e. Nilaparvata lugens, Cnaphalocrocis medinalis and Chilo suppressalis) with minimal impact on natural enemies via selection of a specific entomopathogenic fungal strain for use as a biological control agent. In large-scale multiyear field applications, Metarhizium anisopliae CQMa421 was shown to act as effectively as chemical pesticides for pest control. Rice pest control applications in all major rice-producing provinces in China covering > 6000 hectares, performed over a period of 8 years (2011–2018), showed equal rice harvest yields between the use of the fungal pathogen versus chemical pesticides. More importantly, the use of the specific fungal pathogen isolated by this strategy resulted in an increase in beneficial insects and other animals. These long-term field evaluation data and large-scale application results demonstrated the feasibility of shifting from chemical dependency to more nuanced approaches for pest control for maintaining agricultural productivity while protecting natural enemies. With this strategy, new specific fungal strains can also be isolated to control the main pests of other crops.