Weak interaction between flocculants and antibiotics is a limitation in the flocculation of combined contaminants of heavy metals and antibiotics. To solve this problem, a novel chitosan-based flocculant (BDAT-CTS) owning functional groups of aromatic rings, which possessed potential to interact with other aromatic rings in antibiotics, was synthesized and applied to remove Cu(II) and tetracycline (TC) from water. Effects of pH, flocculant dosage and initial contaminant concentration were studied in detail. In comparison with previous reported chitosan-based flocculant without aromatic rings structure, BDAT-CTS enjoyed significantly enhanced removal efficiency in the treatment of binary contaminants. The highest removal efficiencies of TC and Cu(II) could reach to 98.8% and 94.0%, respectively, under the corresponding optimal conditions. The improved performance was attributed to the strong triangle pairwise interactions among BDAT-CTS, Cu(II) and TC according to flocculation mechanism investigation: besides charge attraction and coordination of BDAT-CTS–Cu(II), and coordination of Cu(II)–TC, there also exists π–π stacking between the triazine rings in BDAT-CTS and the aromatic rings in TC. The current work provided valuable guidance in the design of eco-friendly polymeric flocculants in the treatment of combined water contamination of heavy metals and antibiotics.