Fungal plant pathogens constantly evolve and deploy novel peptide and metabolite effectors to break down plant resistance and adapt to new host plants. The blast fungal pathogen Pyricularia oryzae is a single species subdivided into multiple host-specific lineages. This host specialization is likely due to secreted effectors, including metabolite effectors. Here, we mined 68 genomes of P. oryzae, belonging to six host-specific lineages, to identify secondary metabolite (SM) biosynthetic gene clusters (BGCs) associated with host specialization. A similarity network analysis grouped a total of 4,501 BGCs into 283 gene cluster families (GCFs), based on the content and architecture of the BGCs. While most of the GCFs were present in all the P. oryzae lineages, two were found specifically in the Oryza lineage and one was found in the lineage specific to Triticum, Lolium and Eleusine hosts. Further analysis of the phylogenetic relationships between core biosynthetic genes confirmed that a BGC, comprising a reducing polyketide synthase (PKS) gene (MGG_08236) and four putative tailoring genes, was present only in the Oryza lineage. The predicted BGC was found expressed specifically during host penetration and colonization. We propose that this Oryza lineage-specific BGC is likely associated with a metabolite effector involved in specialization of P. oryzae to rice host. Our findings highlight the importance of further exploring the role of metabolite effectors in specialization of the blast fungus to different cereal hosts.