In this study, CoFe2O4@methycellulose (MC) was prepared as a novel magnetic nanocomposite by a facile, fast, and new microwave-assisted method using iron and cobalt salts in the presence of MC as a green biopolymer in alkaline medium and was then structurally evaluated by FESEM, EDS, Mapping, BET, VSM, XRD, TGA, and FTIR. Effective parameters on tetracycline (TC) removal such as pH, initial TC concentration, adsorbent dosage, and contact time were examined. The central composite design (CCD)-based response surface methodology (RSM) was employed to design the experiments and find optimal conditions. CoFe2O4@MC was synthesized with the particle size of about 50 nm, magnetic properties, and high specific surface area. The maximum TC adsorption efficiencies using CoFe2O4@MC from synthetic and real wastewater samples under optimal conditions were 79.45% and 74.85%, respectively. The data of TC adsorption on CoFe2O4@MC were fitted well with pseudo-second order kinetic and Langmuir isotherm models. The results of thermodynamic data indicated the exothermic and spontaneous nature of TC adsorption process using CoFe2O4@MC. CoFe2O4@MC showed high efficiency and chemical stability after 5 runs. Therefore, CoFe2O4@MC nanocomposite can be applied as a good and practical adsorbent for removing TC from synthetic and real wastewater.