Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS) are widely used and considered as emerging persistent pollutants, posing a potential threat to the aquatic ecosystem due to their metabolic toxicity. However, the effects of early-life PFOA and PFOS exposure on metabolic disruption and underlying mechanisms are not fully understood. Therefore, we investigated the effects of early-life PFOA or PFOS exposure on lipid accumulation, feeding behaviors, fatty acids composition, and possible genetic regulation using the nematode Caenorhabditis elegans as an in vivo model. Our results showed that low concentrations of PFOA and PFOS (0.1 and 1 μM) induced obesity in C. elegans, which was not due to the increased feeding rate. The altered fatty acid composition illustrated the decrease of saturated fatty acids and the increase of polyunsaturated fatty acids. Furthermore, the mutant assay and mRNA levels revealed that fatty acid desaturation related genes mdt-15, nhr-49, fat-6 as well as fatty acid (fasn-1) and triglyceride (TG) (dgat-2) synthesis related genes, were associated with the increased body fat, TG, and lipid droplet (LD) contents in C. elegans exposed to PFOA and PFOS. Hence, this present study provides the genetic regulatory information of PFOA and PFOS induced metabolic disruption of lipid metabolism and obesity.