Coagulation is a common method used to remove suspended particulate matter (SPM) from the water supply. SPM has preferable adsorption ability for antibiotics in water; therefore, SPM adsorption and coagulation may be a possible way to remove tetracycline (TC) from water. This study carried out coagulation experiments combining SPM collected from a natural lake at a location with three common coagulants—polyaluminum sulfate, polyaluminum chloride, and polyferric sulfate—under different pH values, exploring the adsorption of TC by SPM, coagulation of SPM with TC, and the primary influencing factors of this process. The maximum removal rate of TC can reach 97.87% with an SPM concentration of 1000 mg/L. Multi-factor analysis of variance showed the importance of various TC removal factors, which were ranked as follows: SPM concentration ≫ initial TC concentration > type of coagulant > pH values. The higher the SPM concentration, the better the TC removal (p < 0.001). Fourier infrared spectroscopy results demonstrated the strong adsorption effect of SPM on TC after being combined with a coagulant, and scanning electron microscopy also indicated that SPM becomes effective nuclei in the coagulation process, which is a possible reason for better TC removal. However, the effluent turbidities under 1000 mg/L SPM concentrations were high without coagulant aid. With the addition of coagulant aid anion polyacrylamide, the TC removal remained unchanged, effluent turbidity significantly reduced, and the TC desorption became low. These results indicate that applying SPM from natural lakes in the coagulation process could potentially remove TC in water.