As exploration of deep and ultra-deep becomes more active, the utilization of acrylamide-based polymers as drilling fluid additives in challenging subsurface conditions, particularly at high temperatures, is growing. In this study, various monomers including acrylamide (AM), 2-acrylamido-2-methyl-1-propanesulfonic acid (AMPS) and dimethyl diallyl ammonium chloride (DMDAAC) were used to synthesize an acrylamide-based polymer ZP1. Subsequently, 2.5 wt% aqueous solution of polymer ZP1 was subjected to a high-temperature degradation test at temperatures of 150, 180, 200, 220, and 240 °C, respectively. The degradation behavior of the polymer in aqueous solution and drilling fluid was investigated using various analytical techniques, including FT-IR, 1H NMR, XPS, GPC, TG-IR, and SEM. The research results indicate that the degradation temperature of the solid polymer sample was 258 °C, while in the solution at a temperature higher than 200 °C, the hydrolysis and imidation reaction in the polymer molecular chain was accelerated, which caused the main chain of the polymer to break easily. When the molecular weight (Mn) of the polymer decreased to less than 10,000, the protective influence of the polymer on the drilling fluid was lost, resulting in deterioration of the performance of the drilling fluid. However, the functional groups (amide groups, sulfonic acid groups, and quaternary ammonium groups) on the molecular chain of the polymer were retained.