This work investigates the development of copper-based metal organic framework (CuMOF)–chitosan (CS)–hydroxyapatite (HAp) hybrid catalysts to enhance the photocatalytic degradation of ciprofloxacin (CIP) in contaminated water. The integration of these materials resulted in a hybrid catalyst with exceptional photocatalytic activity, showing promise for addressing antibiotic-induced water pollution. Characterization techniques like Scanning Electron Microscopy (SEM), Energy Dispersive Spectroscopy (EDS), Fourier Transform Infrared Spectroscopy (FTIR), and X-ray Diffraction (XRD) confirmed that ultrasound-assisted synthesis improved the physicochemical properties of the catalyst, including higher surface area, better morphology, and greater structural stability. Photocatalytic tests demonstrated that both conventional and ultrasound-assisted catalysts effectively degraded CIP, with the latter achieving an 83.49% degradation rate at 1 gram catalyst loading after 120 min of exposure, particularly at lower initial CIP concentrations. Increasing the catalyst loading from 0.5 g to 1.0 g provided more active sites, accelerating pollutant breakdown. Key factors such as catalyst loading, pollutant concentration, and exposure time were identified as critical to the degradation process, with statistical analysis underscoring the importance of optimizing these variables for maximum efficiency. The study highlights the potential of CuMOF-CS-HAp hybrid catalysts in environmental remediation, particularly for tackling antibiotic pollution in aquatic environments. It also emphasizes the role of ultrasound-assisted synthesis in boosting photocatalytic performance, contributing to the development of advanced materials for water purification.