In the water treatment process of natural water bodies, a large amount of dredged slurry with high water content is generated and required for treatment. The coagulation–flocculation method can improve the efficiency of separation, and a suitable scheme is of great significance. It is unclear whether there is a significant difference in flocculation and separation of dredged slurries from different sources and which constituents dominate this process. Facing these problems, the tests were conducted for dredged sediments from 10 different sources, including rivers, lake, and ocean. Under the same flocculation conditions, the difference in the increment of particle size d10, the specific resistance of filtration, and the suspended solids (SS) of the supernatant after sedimentation are 0–4.6 times, 0–2.4 orders of magnitude, and 0–4 orders of magnitude, respectively. It was found that the main constituents in the dredged slurries, such as clay minerals, fulvic acid and humic acid, impact on flocculation and separation effects by affecting the zeta potential of the particles. However, there is no single constituent in the dredged slurry which dominates the flocculation and separation effect. When these constituents are incorporated, the zeta potential exhibited in the slurry determines the difference in flocculation and separation effects.