In order to enhance the profitability of dairy buffaloes, it is necessary to develop an understanding of the factors affecting their reproduction and milk production ability. Thus, the objective of this study was to elucidate the economic impacts of calving season and parity on reproduction and production indices of Egyptian dairy buffaloes (1180) reared under subtropical environmental conditions. Buffaloes calving in the autumn season had lesser days open, calving interval, and service per conception (108.25 days, 414.16 days, and 1.67, respectively), while spring calvers showed the greater calculations (210.27 days, 522.82 days, and 2.39, respectively). The buffaloes calving for the first time had the longest days open, calving interval, and number of services per conception among different parities (176.21 days, 490.05 days, and 2.18, respectively), then decreased thereafter. Furthermore, buffaloes calving in the winter season had the significantly highest total milk yield, milk revenue, total revenue, profit, and profit/cost ratio (1981.4 kg, 1769.1 $, 2019.5 $, 662.9 $, and 0.49, respectively) in comparison with other seasons. The total milk yield, lactation period, profit, and profit/cost ratio were increased to reach the peak values in the fourth parity (2051.5 kg, 252.44 days, 674.8 $, and 0.48, respectively), then decreased thereafter. In conclusion, buffaloes at the fourth parity and those calving in the winter season had the best milk yield, milk revenue, total revenue, and profit/cost ratio. Therefore, breeders must pay more attention to calving season and parity as they play an important role in the farm profitability and productivity and should counteract the adverse effects of periodical and seasonal changes. It is recommended to make estrus synchronization for more calvings in the winter season. Finally, choose the best lifetime for keeping the animal in production.