The research of polymerization kinetics and reaction mechanism on flame-retardant polyamide 66 (FRPA66) is of great significance for its industrial production. Here, FRPA66 is prepared by one-step melt polycondensation of nylon 66 salt and a reactive flame retardant DPDA. By exploring the relationship of viscosity-average molecular weight versus reaction time at different polymerization stages, the apparent rate constant of FRPA66 is calculated to be 41.8 dL g−1s−1. Besides, molecular simulation analysis demonstrates that the reaction activation energy of DPDA and nylon 66 salt in pre-polymerization stage is 312.04 kcal/mol, indicating that the pre-polymerization time can be extended to make up for the lack of pre-polymerization power of FRPA66. In the final polymerization stage, reasonable control of releasing pressure and polymerization time can promote the self-condensation of a small part of DPDA, thus improving the molecular weight of FRPA66. Finally, based on the polymerization kinetic and reaction mechanism, FRPA66 containing 5% DPDA can reach V-0 level. Display omitted •Copolymerized flame retardant polyamide 66 was prepared by copolymerization.•The apparent rate constant was fitted to analyze the polymerization kinetics.•The reaction path was analyzed from the perspective of molecular simulation to verify the polymerization kinetics.