A molybdenum disulfide(MoS2)-based core-shell magnetic nanocomposite (Fe₃O₄@MoS₂) was synthesized by the stepwise hydrothermal method. Two-dimension ultrathin MoS₂ sheets with a thickness of approximately 20 nm were grown in situ on the surface of Fe₃O₄ (∼200 nm). They were employed as an adsorbent for the magnetic solid-phase extraction (MSPE) of sulfonamide antibiotics (SAs) from water samples. High-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) was used for SA quantitation. Extraction parameters, including the pH effect, amount of Fe₃O₄@MoS₂, extraction time, temperature, and desorption conditions, were systematically investigated. The electrostatic interaction between the positively charged SAs and negatively charged MoS₂ nanoparticles in the optimal extraction conditions enhanced the adsorption of SAs on the sorbent surface. Under chosen conditions, the proposed strategy achieved wide linear range of 1.0–1000 ng·L⁻¹ SAs, low limits of detection (LOD, 0.20–1.15 ng·L⁻¹, S/N = 3:1), good trueness (recoveries between 85.50–111.5%), satisfactory repeatability and reproducibility (relative standard deviation, <10%, n = 5), and excellent recoveries between 80.20% and 108.6% for SAs determination in spiked waste water samples. The proposed strategy was validated and successfully applied for the analysis of water, milk, pork meat and fish meat. The nanocomposites, which have the combined advantages of magnetic separation and high adsorption affinity toward SAs, are a promising sorbent for antibiotics extraction from real samples.