An aeration control system and method for wastewater are provided. The aeration system, which is connected to an aeration device in an aeration basin, includes a plurality of water quality detectors, at least one pollutant estimate model, and a processing unit. The plurality of water quality detectors are configured to acquire a plurality of water quality data. The plurality of water quality data includes a pre-aeration water quality data and a post-aeration water quality data. The pollutant estimate model is configured to generate a pollutant data according to the pre-aeration water quality data. The processing unit is configured to generate an aeration quantity according to the pollutant data, the post-aeration water quality, and an effluent water quality setting, and transmitting the aeration quantity to the aeration device.