The arbitrary selection of flocculants is a prominent problem in the application of engineering waste slurry dewatering. To address this issue, typical clay minerals were focused and the differences in flocculant selection criteria and coagulation dewatering mechanisms were systematically explored. Capillary water absorption time (CST) and specific resistance (SRF) were adopted as evaluation indicators, and microscopic characterization methods such as thermogravimetric analysis (TGA) and scanning electron microscopy (SEM) were employed as supplements. The results indicate that the particle bound water content is identified as the key determinant for flocculant selection. Specifically, cationic polyacrylamide (CPAM) is suitable for high binding water clay (such as montmorillonite). CPAM can effectively weaken the bound water film through electrical neutralization. After CPAM treatment, the CST of montmorillonite slurry decreases significantly from 61.8 s to 8.2 s, and the specific resistance decreases by 77%. Conversely, nonionic polyacrylamide (NPAM) should be used for clay with medium-to-low bound water content, such as kaolinite and illite. NPAM mainly forms porous flocs of clay particles through adsorption bridging, which facilitates the discharge of free water. After NPAM treatment, the CST of kaolinite slurry and illite slurry decreases to 7.8 s and 18.3 s, respectively, and the specific resistance of both decreases by more than 73%. Given that the properties of inorganic slurry are mainly determined by its dominant mineral, the research results provide theoretical guidance and a fundamental basis for efficient flocculation selection in engineering applications based on major mineral composition.