The increasing reliance on aquaculture for sustainable protein production highlights the need for responsible antibiotic use to manage bacterial infections, particularly in intensive farming systems. This study investigated the effects of three FDA-approved antibiotics (Aquaflor®, Romet®, Terramycin®) at common fish bacterial disease outbreak temperatures (20 °C, 25 °C, and 30 °C) on the microbiome and resistome of aquaculture water using a catfish model system. Metagenomic analyses evaluated the abundance, diversity, and mobility of antimicrobial resistance genes (ARGs) and antibiotic-resistant bacteria (ARB). The impact of temperature on Aquaflor- and Romet-induced changes in ARG abundance, richness, and resistome composition followed a U-shaped trend, with the least effect observed at 25 °C. Of the three antibiotics tested, Terramycin exerted the most significant influence on the water microbiome and resistome, enriching tetracycline resistance genes and co-selecting for floR, sul, and dfrA genes. Temperature also induced notable shifts in the ARB population, with Mantel tests revealing strong correlations between ARG profiles and changes in the overall bacterial community and ARB populations. While certain ARG classes consistently remained associated with specific host phyla, others shifted, highlighting the potential for horizontal gene transfer (HGT) as a critical mechanism for disseminating resistance genes like tet(C), particularly after antibiotic treatment. This is further supported by the observed reduction in plasmid numbers following treatment, which coincided with increased HGT events. Our findings highlight the pivotal role of temperature in influencing resistome dynamics, emphasizing the importance of accounting for environmental factors when applying antibiotics to effectively mitigate antimicrobial resistance in aquaculture systems.