Rice blast, caused by Magnaporthe oryzae (M. oryzae), is a severe threat to rice production globally. The pathogen counters rice immunity by secreting effectors that disrupt host defenses. In this study, we conducted a comprehensive genome-wide screening to identify candidate secreted effector proteins (CSEPs) in M. oryzae. Using a new bioinformatics pipeline, we predicted 577 CSEPs and analyzed their sequence features and functional annotations. We found that these effectors have distinct sequence signatures, such as high cysteine content, and are involved in infection and immune suppression. Phylogenetic analysis revealed M. oryzae's close relationship with other pathogenic fungi and the conservation of certain CSEPs across species. Expression analysis during infection indicated a role of CSEPs in the pathogenic process and the ability to inhibit plant necrosis. Finally, we validated the function of three candidate effector proteins through gene disruption mutant analysis including pathogenesis testing in rice. This study provides a foundation for understanding M. oryzae pathogenicity and may aid in developing resistance strategies against rice blast.