Aquaculture is a key technology in seafood production because capture fishery production remains at the same level despite increasing demand for seafood. Thus, genetic breeding is necessary to efficiently obtain fish and shellfish products in aquaculture. Although selective breeding has been the most popular and widely used method for both plants and animals, it usually takes a long time to establish strains with desirable traits. In contrast, chromosome set manipulation and genome manipulation including transgenesis and genome editing allow expression of desirable traits for aquaculture within a comparatively short period. The former can induce polyploids and artificial parthenogenesis. Triploid fish and shellfish have been used for aquaculture due to their sterility. Sterile triploids show advantages in high flesh quality during spawning season compared to fertile diploids, and in biological containment to avoid genetic contamination of wild populations. The latter can induce individuals with desirable traits by direct alteration of the genome, such as insertion of foreign genes to obtain additional traits by transgenesis and mutation of the indigenous genome to enhance desirable traits by genome editing. Here, we review applications of polyploids in aquaculture and current topics of genome manipulation in fish genetic breeding.