The prevalence of antibiotic resistance genes in microbial communities from sewage wastewater streams and from offshore marine sediments in the vicinity of sewage wastewater outfalls in Southeast Florida was investigated from June 2018 to March 2019. Sediment and wastewater samples were analyzed for 15 different antibiotic resistant gene targets via polymerase chain reaction (PCR) presence/absence assays in Southeast Florida coral reef environments. Data collected from five sites (Broward North Wastewater Treatment Plant (WWTP), Broward North WWTP Outfall, Haµlover (Miami-Dade North) Outfall, Hollywood Outfall, Hollywood WWTP, and Miami-Dade North WWTP) illustrated widespread prevalence of antibiotic resistance genes in these microbial communities with the highest concentrations occurring in the sewage wastewater stream and in close proximity to the outfall pipe and outfall. Data indicated seasonal (wet versus dry season) trends and potential public and ecosystem health risks. Additionally, a reef in the Florida Keys was evaluated during the wet season using the same tools and approach prior to and after diseased corals were treated with amoxicillin. Resistance to amoxicillin was only observed in the post-treatment sample set.