ABSTRACT Fusarium disease is an infectious condition that occurs in the cultivation of kuruma shrimp ( Penaeus japonicus ), primarily presenting as lesions in the gills. These lesions contain proteolytic enzymes of likely bacterial origin. This is the first study to demonstrate fungal–bacterial mixed infection in gill lesions of Fusarium‐infected kuruma shrimp. Tenacibaculum spp. showing proteolytic activity were isolated from the lesions, whereas Fusarium spp. showed no such activity. Two Tenacibaculum strains were identified as Tenacibaculum mesophilum based on whole‐genome sequencing (WGS) using MiSeq and GridION. Comparative analysis with the type strain DSM 13764 revealed > 95% nucleotide identity and 82.7% DNA–DNA hybridization similarity, with average genome coverage of 250×. Genomic analysis predicted that the genomes encode multiple protease and antibiotic resistance genes. Histopathology and SEM revealed that Fusarium hyphae had penetrated gill tissue, accompanied by infiltration of blood cells. Both fungal hyphae and T. mesophilum co‐localised around gill cells. Bacterial diversity, assessed by 16S rRNA gene sequencing (V4 region), declined with tissue disintegration. Immune‐related host genes such as anti‐lipopolysaccharide factor (ALF) and lactate dehydrogenase (LDH) were upregulated, suggesting innate immune activation. These findings provide novel insights into the disease pathogenesis and contribute to the establishment of early detection systems and biosecurity‐based control strategies.