Huanglongbing (HLB), associated with Candidatus Liberibacter asiaticus (CLas), has severely impacted global citrus production, with no economically viable control measures currently available. This study explored microwave treatment at 2450 MHz as an innovative physical method for HLB control, combining pathogen elimination efficacy with metabolomic analysis. In controlled experiments, 36 HLB-infected citrus plants were treated with 500 W or 250 W microwave irradiation and underwent 10 cycles, achieving up to 99.83% reduction CLas titer. Non-targeted metabolomic analysis identified 15 significantly altered metabolites, including upregulated beta-caryophyllene and lysophosphatidylinositols, and downregulated 5′-S-methyl-5′-thioadenosine. The results indicate that microwave treatment effectively suppressed CLas while simultaneously triggering citrus physiological metabolic changes. These findings suggest that microwave treatment could serve as a sustainable alternative to chemical controls. However, further optimization of parameters, such as wavelengths, voltages, currents, and safety protocols, will be essential for practical field implementation.