Date palm dust mites are important pests severely infesting valuable nutritious fruits (dates) of date palm. In search of an alternative to acaricides, joint action of Metarhizium anisopliae EBCL 02049 spores and 1-Chlorooctadecane was evaluated as a potential candidate for the management of Oligonychus afrasiaticus through natural products. In this regard, in vitro tests were performed to evaluate the interaction of M. anisopliae spores with multiple doses of 1-Chlorooctadecane (0.8, 1.6, 2.4, 3.2, and 4.0 mg/mL). Compatibility bioassay results evidenced from vegetative growth (77.7–84.40 mm), sporulation (5.50–7.30 × 106 spores/mL), and germination (96.70–98.20%), revealed that all the tested doses are compatible (biological index > 82) with the spores of M. anisopliae. The impact of combined treatment of spores with 1-Chlorooctadecane in different proportions (Scheme I, II, III, and IV) compared to their sole application against O. afrasiaticus was evaluated by concentration–mortality response bioassays. Results showed that all the combined treatments revealed high mortality compared to the sole application, which showed relatively slow mortality response over time. Toxicity recorded from Scheme IV combinations (80% 1-Chlorooctadecane: 20% Spores), exhibited strong synergistic interaction (joint toxicity = 713). Furthermore, potent interactions have overcome the host antioxidant defense at the final stage of infection by tremendously reducing catalase, and superoxide dismutase activities. These experiments demonstrated fungal–toxin joint synergistic interaction as a promising date palm dust mite management option.