Elicitors provide a broad spectrum of systemic acquired resistance by altering the physical and physiological status of the host plants and, therefore, are among the most successful directions in modern pesticide development for plant protection. To develop a novel elicitor with highly systemic acquired resistance, two series of thiazole- and oxadiazole-containing thiadiazole derivatives were rationally designed and synthesized according to the principle of combination of bioactive substructures in this work. Their structures were characterized by (1)H nuclear magnetic resonance (NMR), infrared (IR), high-resolution mass spectrometry (HRMS), or elemental analysis. Their potential systemic acquired resistance as an elicitor was also evaluated; bioassay results indicated that, among the 23 compounds synthesized, three compounds, 10a, 10d, and 12b, displayed better systemic acquired resistance than the positive control, tiadinil, a commercialized 1,2,3-thiadiazole-based elicitor. In addition, three other compounds, 10f, 12c, and 12j, exhibited a certain degree of fungus growth inhibition in vitro or in vivo. Our results demonstrated that, in combination of bioactive substructures is an interesting exploration for novel pesticide development, thiazole- and oxadiazole-containing thiadiazole derivatives are potential elicitors with good systemic acquired resistance.