Simple SummarySoybean meal is an effective protein source in aquafeeds and is characterized by high protein content, high digestibility, reasonable price, and stable supply. The quality of soybean meal varies with factors such as seed genotype, soil type, planting area, processing conditions, storage conditions, etc. Differences in soybean meal quality may lead to differences in the production performances of animals. For this reason, we investigated the nutrient composition, anti-nutritional factors and physicochemical properties of different soybean meals produced on the same production line with soybeans from different origins, and compared the effects of different soybean meals on the physiological characteristics of Nile tilapia (Oreochromis niloticus GIFT). This study identified key indicators that could distinguish the quality of soybean meals, and established a correlation model between quality indicators of soybean meal and the growth performance of Nile tilapia. These results are of great significance for evaluating the quality of soybean meals and promoting the efficient application of soybean meal in aquafeeds.Soybean meal (SBM) is the most important plant protein source in animal feed. This study investigated the characteristics of different SBMs, produced by soybeans from America and Brazil (SBM-A and SBM-B) in 2017–2021 under the same controlled conditions. The effects of different SBMs on the growth performance of Nile tilapia (Oreochromis niloticus, GIFT) and apparent digestibility coefficients (ADCs) of nutrients and energy were studied. The results showed that protein dispersibility index (PDI), urease activity (UA), glycinin and fiber were the four primary key indicators for distinguishing the characteristics of the tested SBMs. The meta-analysis results suggested that UA, glycinin, and fiber showed a negative effect on the survival rate (SR) and weight gain rate (WGR) of the Nile tilapia, whereas β-conglycinin, PDI, and nitrogen solubility index (NSI) had a positive effect on the SR and WGR of the fish. The ADCs of dry matter, the gross energy, phosphorus, crude protein, valine (Val), lysine (Lys), histidine (His), serine (Ser), and glutamate (Glu) of the Diet-A group (SBM-A inclusion) were significantly higher than those in the Diet-B group (SBM-B inclusion) (p < 0.05). However, no significant difference was found in ADCs of macro-nutrients between the two SBMs (p > 0.05). Overall, PDI, UA, glycinin, and fiber were the main indicators reflecting the characteristics of the tested SBMs, and UA, glycinin, β-conglycinin, and PDI had the greatest impact on the growth performance of Nile tilapia in this study. PDI was a more sensitive indicator than NSI for representing the protein quality of SBM.