13X zeolite was synthesized for removal of tetracycline from aqueous solution. To improve the removal efficiency, FAU zeolite was exposed to ion exchange process with Cu+2 . The experiments were designed by the Design-Expert 7.0.0 software. The effect of experimental parameters including initial tetracycline (TC) concentration (50, 156.5, 525, 893.5, 1000 ppm) Cu+2 dosages (0, 0.3, 1.3, 2.2, 3 g/g) solution pH (2, 3, 6.5, 10, 11) and contact time (20, 34.6, 85, 135.4 min) was evaluated on TC removal efficiency. For minimizing the number of experiments for a complete evaluation, response surface methodology and central composite design were applied by means of Design-Expert 7.0.0 software. Results revealed that FAU zeolite adsorbent was effective in removal of tetracycline, where the removal efficiency was 85%. In fact, by increasing initial TC concentration from 156.5 to 890 mg/L, the removal efficiency was increased, while further increase in initial TC concentration over 890 mg/L did not cause a significant enhancement in its removal efficiency. Amount of exchanged Cu to 1.75 g/g had a positive effect on the removal efficiency but in over 1.75 g/g dosages, the removal efficiency showed a decreasing trend. The Design-Expert 7.0.0 software reported that the optimal operating conditions are TC concentration—810.5 ppm, Cu+2 dosages—0.6 g/g, solution pH—5.3, and contact time—113.6 min. The adsorption isotherms were fitted by Sips and Freundlich and Redlich–Peterson models. Finally, the adsorption kinetics were also studied by pseudo-second-order equation.