<p>Antibiotic residues in the environment threaten ecosystems and human health. In this study, single antibiotics (ciprofloxacin (CIP), oxytetracycline (OTC), and sulfathiazole (STZ)), binary antibiotic mixtures (COII and CSII), and a ternary antibiotic mixture (COSIII) were used as target contaminants, and the Guideline 106 batch equilibrium method was used to investigate the adsorption processes and influencing factors at the water–sediment interface. The results revealed that the adsorption capacity of the sediments for the three antibiotics followed the order OTC &gt; CIP &gt; STZ. The adsorption kinetics of antibiotics in sediments conformed to the pseudo-second-order kinetic model (<i>R</i>^<i>2</i> &gt; 0.999), whereas the adsorption isotherms fit both the Langmuir and Freundlich equations (<i>R</i>^<i>2</i> &gt; 0.91). In the COII and CSII systems, the adsorption of OTC and STZ by the sediments was slightly inhibited by CIP, reducing their equilibrium capacities by 29.29% and 45.50%, respectively. For the adsorption of single antibiotics, the equilibrium adsorption capacity and total adsorption amount followed the order OTC &gt; CIP &gt; STZ, whereas for mixed adsorption, the total adsorption amount followed the order COSIII &gt; COII &gt; CSII. pH had a significant effect on the competitive adsorption between CIP and OTC but did not alter the inhibitory effect of CIP on STZ. Low and high concentrations of the coexisting cations K⁺, Ca²⁺, and Mg²⁺ synergistically enhanced and competitively inhibited adsorption, respectively, whereas Al³⁺ consistently demonstrated a pronounced competitive inhibitory effect.</p>