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A cross-sectional study was conducted to assess antibiotic usage, residues, resistance and drivers of their emergence in fish aquaculture in Northern Nigeria between 2019 and 2020. A structured questionnaire was administered to 151 randomly selected farmers. Fish, column and wastewater samples were analysed with enzyme link immunosorbent assay (ELISA) for residue detection and quantification. We performed descriptive and analytic statistical analyses. All selected farmers participated, 78.1% used antibiotics in ponds. Majority (77.1%) of the farmers did not know what antibiotic misuse entailed and 73.3% mentioned that antibiotic misuse and overuse cannot predispose to residues and resistance. The most frequently used antibiotics were tetracyclines (TCs) (99.2%). Significant risk routes for residue and resistance spread were: contaminated fish and its products ingestion, direct contact with fish and fomites contaminated as well as water and aerosols contaminated in the pond environment. Significant social and cultural that influenced residue and resistance development include antibiotics misuse/overuse (Odds Ratio [OR] = 3.8; 95% confidence interval [CI]: 1.62-8.74) as well as poor education and expertise of the farmers (OR = 2.9; 95% CI: 1.24-6.94). The mean TCs residues level in column and wastewater was 123.6 ± 18.2 μg/kg-1. Poor knowledge and attitudes regarding antibiotic usage were identified. Adequate antibiotic stewardship should be promoted through farmers' education. Identified social and cultural factors can be mitigated through the 'One Health' approach.