Abstract: Oplegnathus punctatus is a marine fish species with great potential for aquaculture development. However, its industrialization is severely threatened by diseases caused by pathogens such as Edwardsiella tarda, and relevant research on disease-resistant breeding remains unsufficient. Based on the establishment of family lines, we conducted the first genetic selection and breeding of disease-resistant and fast-growing O. punctatus families, having successfully established a total of 57 F₂ families in 2023 using the first-generation (F₁) families developed in 2019 as broodstock. Among them, 41 families (Comprising 1 406 individuals, with 20–60 fish per family) were selected for an artificial challenge with Edwardsiella tarda. Three highly resistant families (F2309, F2324, F2354) were identified, showing survival rates exceeding 40%. Systematic analysis of body mass data from the 41 families further revealed 4 fast-growing families (F2331, F2324, F2351, F2307) and 12 relatively fast-growing families. Best linear unbiased prediction (BLUP) analysis indicates that the heritability for resistance to E. tarda was 0.151±0.046, suggesting low-to-moderate heritability. The findings support the effectiveness of family-based selection for the genetic improvement of this trait. By integrating estimated breeding values and resistance phenotypes, family F2354 demonstrated the most outstanding resistance performance, with both its male and female parents ranking first in estimated breeding value among all parents of the same sex. The study provides novel methodologies and reliable breeding materials for the selection of disease-resistant varieties in O. punctatus.