Although various antibacterial strategies have been developed, antibiotic chemotherapy remains the primary clinical treatment for bacterial infections. To address the limitations associated with the traditional antibiotic therapy, like burst drug release, rapid drug clearance, and the emergence of drug resistance, it is highly desirable to develop drug release systems that can realize controlled and sustained drug release to enhance the therapeutic efficacy. Herein, we present a novel drug release system, CIP@SU-102, which shows superior and long-lasting antibacterial activity. CIP@SU-102 was readily fabricated by the encapsulation of ciprofloxacin (CIP), a cationic broad-spectrum antibiotic, into an anionic Zr-based metal-organic framework SU-102 through ion-exchange. Notably, the loading capacity and efficiency of CIP were impressively high, reaching 33.3% and 66.8%, respectively. In vitro assays demonstrated that CIP@SU-102 has superior and prolonged antimicrobial activity against Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus aureus) bacteria, including the methicillin-resistant Staphylococcus aureus (MRSA). Remarkably, CIP@SU-102 could retain its antibacterial efficacy even after continuous drug release for 20 days. In vivo assays verified that CIP@SU-102 could significantly accelerate infected wound healing because of its sustained drug release properties. Due to the low cost and biocompatibility of SU-102 as well as the affordability of ciprofloxacin, CIP@SU-102 is a very promising antibacterial agent for long-lasting bacterial disinfection and boosting infected wound healing in actual clinical applications. This work highlights the potential of the metal-organic framework-based drug release systems for sustained antimicrobial therapy.