To assess Escherichia coli (E. coli) persistence in dairy manure, bench scale experiments were conducted under aerobic and anaerobic environments. The changes in E. coli levels in dairy manure were assessed at moderate (25 °C), mesophilic (37 °C), and thermophilic (52.5 °C) temperatures. The inactivation of E. coli at moderate, mesophilic, and thermophilic temperatures were described by linear regression equations. Subsequently, double-exponential kinetic models were developed to describe the E. coli decay curves under aerobic and anaerobic environments. The kinetics models were used to estimate E. coli log reductions at various temperatures. Results showed that the double-exponential kinetic models performed well while calculating E. coli reductions in dairy manure over the incubation period. In addition, we evaluated digestate to compare the changes in total solids and volatile solids, total organic carbon, total nitrogen, pH, and oxygen reduction potential levels in aerobic and anaerobic conditions under various temperatures. We anticipate that the results presented here will be useful for enhancing the understanding of pathogen reduction in anaerobic and aerobic processes during dairy manure treatment.