In order to improve the flame‐retardant properties of epoxy resin (EP) without sacrificing the mechanical properties, a high‐efficient P/N/S‐containing reactive flame retardant (VTZD) was synthesized by a facile one‐pot method from vanillin, 2‐aminobenzothiazole and 9,10‐dihydro‐9‐oxa‐10‐phosphaphenanthrene‐10‐oxide (DOPO), and used in epoxy‐amine thermosets. When 5 wt% of VTZD was added with merely 0.31 wt% of phosphorus, the LOI value of cured resins increased to 32.7%, and the thermosets achieved a UL‐94 V‐0 rating. Furthermore, the peak heat release rate and the total heat release of the VTZD‐modified EP decreased by up to 34.66% and 32.49%, respectively, in comparison to those of the original EP. Subsequently, the residual char morphology and structure of epoxy thermosets were investigated, as well as the pyrolysis behavior of VTZD. The flame‐retardant mechanism was discussed in detail, and it confirmed that VTZD exhibited a bi‐phase flame retardant effect. In addition, the mechanical properties of the cured products were well maintained and even improved. All the results demonstrated that the VTZD was a bio‐based high‐efficiency flame retardant for EP with a broad prospect in practical applications.