The invention provides a water quality regulation and control system and method for factory aquaculture. A dissolved oxygen prediction content at predicted time after a first preset time period is predicted according to water body parameters through collection of the water body parameters of a culture pond, the first preset time period is a lag time period of an aeration process, an oxygen consumption factor at the predicted time is determined according to culture behavior parameters and a fish activity law, an oxygen supply amount at the predicted time is determined according to the dissolvedoxygen prediction content, a dissolved oxygen standard content in a water quality standard for fisheries in China and the oxygen consumption factor, an oxygen supply regulation and control command isgenerated according to the oxygen supply amount at the predicted time, and a dissolved oxygen content of a water body in the culture pond is adjusted according to the oxygen supply regulation and control command; and namely an oxygen supply regulation and control command at current time is determined according to the dissolved oxygen prediction content at the predicted time and the oxygen consumption factor at the predicted time, so that aeration can be performed on the water body before an oxygen content in the water body is detected to be too low, the possible condition of fish death due tolack of oxygen is avoided, and loss caused by fish death due to the lack of the oxygen is avoided.