Rubber toughened poly(2,6-dimethyl-1,4-phenylene oxide)/polyamide-66 (PPO/PA-66) blends are important engineering plastics in automobile industries. They are generally fabricated by two step procedure. First, a maleation of PPO is carried out to fabricate a maleic anhydride grated PPO (PPO-g-MA) as a reactive compatibilizer. Then, PPO/PA-66/elastomer blends are fabricated with the PPO-g-MA. In this study, we proposed a novel one step method in which maleation and reactive blending occur simultaneously in a twin screw extruder. Physical properties of the blends by both methods show similar values. Therefore, we can successfully produce PPO/PA-66/elastomer blends with a reduced production cost without deteriorating the physical properties.