In this study, the coadsorption behaviors of Cu(II) and sulfamethoxazole (SMZ) onto a polyamine-modified resin (PSA) have been systematically investigated. The synergistic adsorption of Cu(II) and SMZ by PSA has been observed, especially at low concentrations. The adsorption amount increased by 9.1% for SMZ and 20.9% for Cu(II) when they coexisted. Herein, two bridging mechanisms were revealed using sequential adsorption tests and characterizations (Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, pH monitoring, and Density-Functional-Theory calculations). Cu(II) preloaded in the resin phase could serve as new sites for SMZ, thereby forming surface ternary complexes ([-N-Cu]-SMZ), in which Cu(II) may coordinate with both the heterocyclic N and sulfonamide N groups in SMZ. Meanwhile, the adsorption of anionic SMZ onto the surface -NH3+ sites facilitates more Cu-N coordination binding due to the electrostatic shielding effect. Furthermore, we have quantitatively estimated the adsorbate distribution in the resin phase during coadsorption. In addition, approximately 96.7% SMZ and 99.8% Cu(II) could be successively recovered with NaClO3 followed by HCl. Cu (II) could also enhance the adsorption of other sulfonamides onto PSA by a maximum of 61.4%. These results supply more understanding of the mutual interaction between heavy metals and sulfonamides in amine-containing adsorbents and demonstrate the potential application of these adsorbents for controlling the combined pollution.