Antimicrobial resistance (AMR) in aquaculture has emerged as a critical global challenge driven by the excessive and often unregulated use of antibiotics in fish and shrimp farming, fostering resistant pathogens that threaten animal productivity, environmental integrity, and human health. This article explores how antibiotic residues and resistant bacteria circulate through aquatic ecosystems, seafood chains, and clinical settings, reinforcing a continuous AMR cycle. It emphasizes the One Health approach as an integrated solution that unites human, animal, and environmental sectors to promote responsible antibiotic stewardship, genomic surveillance, farm-level biosecurity, vaccination, probiotics, and sustainable management practices. Strengthening policy enforcement, farmer education, and environmental protection is essential to reducing antibiotic dependency. Coordinated multisectoral action is crucial to safeguard antimicrobial effectiveness, ensure food safety, and secure sustainable aquaculture for future generations.