•A reactive S- & P-containing flame retardant (PDDDS) was designed and synthesized.•The LOI of PA66 with 2% PDDDS increased to 31.6% from 22.7%.•The PHRR, THR, and TSP of PA66-2%PDDDS were depressed by 47%, 45.7% and 65.1%, respectively.•PA66-PDDDS has excellent flame retardant both in gas phase and condensed phase. A sulfur- and phosphorus-containing flame retardant monomer phosphonic diamide, P-phenyl-N, N′-bis(p-sulfanilylphenyl) (PDDDS) was designed, synthesized, and incorporated into polyamide 66 (PA66) through polycondensation to suppress smoke generation upon combustion and achieve satisfactory mechanical properties, a good UL-94 rating (V-0), and a high limiting oxygen index (31.6%). The increased flame retardancy of the PA66-PDDDS copolymer was ascribed to its decomposition into (i) gas-phase P–O and SO2 species scavenging free radicals such as H• and OH• and (ii) condensed-phase products catalyzing the dehydration of PA66 to form char layer. Thus, our work presents a strategy for improving the fire safety of PA66 to significantly expand its practical application value.