The leopard coral grouper, Plectropomus leopardus, belonging to genus Plectropomus, family Epinephelinae, is a carnivorous coral reef fish widely distributing in the tropical and subtropical water of Indo-Pacific Oceans. Due to its appealing body appearance and delicious taste, P. leopardus has become a popular commercial fish for aquaculture in many countries. However, the lack of genomic and molecular resources for P. leopardus hinders its biological studies and genomic breeding programs. Here we report the de novo sequencing and assembly of P. leopardus genome using 10× Genomics and high-throughput chromosome conformation capture (Hi-C) technologies. Using 127.36 Gb 10× Genomics we generated a 902.90 Mb genome assembly with a contig and scaffold N50 of 31.8 Kb and 33.47 Mb, respectively. The scaffolds were clustered and oriented into 24 pseudo-chromosomes with 13.39 Gb valid Hi-C data. BUSCO analysis showed that 95.3% of the conserved single-copy genes were retrieved, indicating a good entirety of the assembly. We predicted 23,234 protein-coding genes, among which 96.5% were functional annotated. The P. leopardus genome provides a valuable genomic resource for genetics, evolutionary and biological studies of this species. Particularly, it is expected to benefit the development of genomic breeding programs in the farming industry.