Three series of co-graft cationic starch (St)-based flocculants with distinct structural characteristics, namely, charge density (CD), graft-chain length (L), and graft-chain distribution (N), were successfully synthesized through graft copolymerization of [(2-methacryloyloxyethyl) trimethyl ammonium chloride] and acrylamide. These St-based flocculants with different molecular structures were used to flocculate various kaolin suspensions with different initial turbidities and a sodium humate (NaHA) aqueous solution. The experimental results indicated that CD contributed to flocculation evidently, whereas average L and its N were insignificant in experimentally measured ranges. On the basis of phenomenological theory, a second-order polynomial equation was used to further quantitatively analyze the effects of the three structural factors on the flocculation performance of these St-based flocculants, which were fully consistent with the experimental results. Besides, the optimal dose and its corresponding removal rate could be predicted exactly, and the flocculation mechanisms were discussed in detail according to the established models. With the combination of floc properties and zeta potentials, the flocculation mechanisms of these St-based flocculants for flocculation of kaolin suspensions and NaHA aqueous solution were mainly ascribed to charge patching and simple charge neutralization, respectively. These results improve the understanding of the structure-activity relationship of these graft St-based flocculants, which is of significant guidance for the utilization and design of novel flocculants.