This work studied the evolution of various indices of a commonly used oil well cement copolymer fluid loss reducer PANI [polymerized by 2-acrylamido-2-methylpropanesulfonic acid (AMPS), N, N-dimethylacrylamide (NNDMA) and itaconic acid (IA)] at ultra-high temperatures, aiming to provide theoretical guidance for the future structural design of ultra-high temperature oil well cement slurry additives. The copolymer solution was placed in a metal aging tank and pressurized with nitrogen, then it was conditioned at a preset temperature (180–240 °C) for different time for further analyses. In terms of physical and chemical parameters, ultra-high temperature aging led to gradual thermal oxidative degradation and group evolution of copolymers, which was manifested by the decrease of apparent viscosity and viscosity-average molecular weight (their values before aging were 8350 MPa s and 3.84 × 105, while decreased to 712.9 MPa s and 9.26 × 104 after aging at 240 °C for 1.5 h, respectively), the removal of side groups and local cyclization. Regarding the application performances, when the aging temperature reached 225 °C or above, both the fluid loss control performance and the thickening performance of copolymer PANI significantly deteriorated. Analysis revealed that the former was caused by the decrease in its molecular weight and adsorptive capacity (resulting from the removal of anionic or polar side groups) of the copolymer; the latter was due to the thickening performance aggravation of the NNDMA unit in the molecular chain, which could be improved by replacing it with the cyclic monomer 4-acryloylmorpholine (ACMO).