Diapause is a programmed developmental arrest process in insects. Diapause can occur at various stages of insect development and is frequently restricted to a specific developmental stage within a single species. In Bombyx mori, embryonic diapause is elicited by the diapause hormone (DH) and DH receptor (DHR) in diapause strains. Nevertheless, the regulatory mechanism through which BmDHR functions as a G protein-coupled receptor (GPCR), to exert other physiological functions in nondiapause silkworms, remains unclear. In this study, we found that BmDHR had 7 alternative splice isoforms. A knockout experiment confirmed that BmDHR mediated the transduction of diapause signals. Interestingly, the loss of BmDHR caused partial precocious metamorphosis and an embryo-lethal phenotype in nondiapause silkworms. An assessment of global transcriptional patterns revealed that BmDHR knockout affected physiological responses induced by manifold cellular processes, including the Toll/immune deficiency (Imd), Wnt, insulin-like growth factor, Hedgehog and P38/mitogen-activated protein kinase (MAPK) signaling pathways. This study expands our knowledge of the physiological roles for DHR in insect growth and development.