The azole pharmacophore is still regarded as a viable lead structure for the synthesis of more effective antifungal agents. In this study, two novel series of imidazole derivatives containing dithiocarbamate (5a–5g) and (benz)azolethiol (6a–6n) side chains that are structurally related to the famous antifungal azole pharmacophore were synthesized, and the structures of them were characterized by spectral (IR, 1 H NMR, 13 C NMR, and MS spectra) analyses. The synthesized compounds were screened in vitro antifungal activity against pathogenic strains fungi. Theoretical ADME (absorption, distribution, metabolism, and excretion) predictions were calculated for final compounds. A molecular docking study of the most active compound with target “lanosterol 14α-demethylase” (CYP51) was performed to unravel the mode of antifungal action. Compound 5e, which features imidazole and 4-methoxybenzyl piperazine scaffolds, showed the most promising antifungal activity with an MIC 50 value of 0.78 μg/mL against C. krusei. Effect of the compound 5e against ergosterol biosynthesis was observed by LC–MS–MS method, which is based on quantification of ergosterol level in C. krusei.