Understanding the antibiotic resistance transmission mechanisms and migration dynamics of antibiotic-resistant bacteria (ARB) in the natural environment is critical given the increasing prevalence of antibiotic resistance. The aim of this study was to examine the fate of sulfonamide-resistant fecal bacteria (E. coli) in an estuary ecosystem and to explore the role and contribution of environmental factors in this process. The prevalence of sulfonamide-resistance status of E. coli was analyzed over different seasons in two estuary systems. Environmental factors and disturbance indices of anthropogenic activities were evaluated by detecting antibiotic concentrations, heavy metal abundance and other physicochemical parameters. The abundances of antibiotic-resistant E. coli were significantly attenuated during land-sea migration suggesting that estuary environments play a natural mitigation role in the contamination of freshwaters by antibiotic-resistant E. coli. Additionally, environmental factors and disturbance indices of anthropogenic activities significantly correlated with the distribution and migration of antibiotic-resistant E. coli in the estuaries. Lastly, simulation experiments suggested differential adaptability between antibiotic-resistant and non-resistant E. coli towards environmental changes in estuary environments. Meanwhile, our results indicate that low concentrations of antibiotics will not increase the competitive advantage of resistant E. coli in estuaries.