A 10-week growth experiment was conducted to evaluate the physiological effects of dietary phosphorus supplementation on red swamp crayfish (Procambarus clarkii) feeding diets with high Clostridium autoethanogenum protein (CAP) levels. Six isonitrogenous and isolipid diets were formulated: The FM diet contained 10% fishmeal, which is equivalent to a dietary phosphorus level of 1.41%, and the CAP, CAPSP1, CAPSP2, and CAPSP3 diets substituted all fishmeal with CAP and supplemented with 0, 2.5%, 3%, and 3.5% Ca(H₂PO₄)₂, respectively (corresponding to dietary phosphorus levels of 0.66%, 1.27%, 1.40%, and 1.52%). A total of 600 crayfish with an initial mean weight of (5.01 ± 0.02) g were selected and randomly assigned to 15 cages for feeding and sampled at the end of the experiment. Results indicate that high-dose CAP replacing fishmeal caused abnormal hepatopancreatic tissue structure in crayfish, exacerbating lipid deposition and oxidative stress. Compared with the CAP group, the specific growth rate (SGR) of crayfish in the CAPSP2 and CAPSP3 groups significantly increased (p < 0.05). The activities of antioxidant enzymes and lipid-degrading enzymes in the hepatopancreas, along with the relative expression of related genes, were significantly enhanced (p < 0.05). Metabolomic analysis demonstrated significant differences in major differential metabolites and metabolic pathways between the CAP group crayfish and the CAPSP2 group (p < 0.05). CAPSP2 group crayfish exhibited a higher content of phosphatidylcholine (PC) and lysophosphatidylcholine (LPC), with significant enrichment in glycerophospholipid metabolism and fatty acid metabolism pathways (p < 0.05). Overall, supplementing dietary phosphorus levels to 1.40–1.52% effectively mitigated growth retardation, oxidative damage, and lipid metabolism disorders induced by high-proportion CAP replacement of fishmeal.