Tetracycline antibiotics (TCs) are typically present at low residue levels in environmental water, necessitating enrichment prior to analysis. In this study, a Cu2+-doped melamine formaldehyde resin (Cu-MFR) was synthesized to enhance the adsorption efficiency for TCs, leveraging the formation of stable Cu2+-TC complexes on the sorbent surface. Then it was used as an adsorbent in solid-phase extraction (SPE) for the enrichment of four TCs from water samples. The optimized parameters for Cu-MFR in the analysis of TCs in environmental water enabled linear detection ranges from 0.20 to 50 ng/mL, with relative recoveries ranging from 79.5% to 97.6% and relative standard deviations ≤ 10.0%, using high-performance liquid chromatography-tandem high-resolution mass spectrometry (HPLC-HRMS). The limits of detection for the four TCs were determined to be between 0.11 and 0.16 ng/mL, indicating its potential for practical application in real sample analysis.