With the increasingly strict requirements on energy saving and environmental protection, the economical, efficient and environment friendly operation of large coal‐fired units are being more and more critical. In light of the technical problems of massive energy consumption and high cost in the operation of the wet desulfurization system in a 1,000 MW ultra‐supercritical boiler, the effects of slurry circulation pump combination, slurry pH and absorption tower liquid level on desulfurization efficiency under different unit loads were tested, and the total operating costs were calculated. The results showed that the power consumption under different conditions could be greatly reduced by changing the combination of slurry circulation pumps. The power cost increases from 1,059.42 to 1,146.99 yuan/hr as the combination of slurry circulation pump changes from AC pump combination to BD pump combination under 1,000 MW, increased by 7.63%. Considering all factors, the combination of BC circulating pump can effectively reduce the power consumption cost and achieve the optimal economical operation under the load of 1,000 and 750 MW. The desulfurization efficiency is in direct proportion to the increase of slurry pH. The optimal pH of slurry under 1,000 MW is in the range of 5.50–5.60, 4.80–4.90 under 750 MW, and 4.50–4.60 under 500 MW. Besides, the absorption tower liquid level has a significant impact on the energy consumption of desulfurization system. With the decrease of the absorption tower liquid level, the power consumption cost of desulfurization system shows a downward trend. To avoid the frequent adjustment of liquid level which may result in safety accidents, the optimal liquid level of absorption tower is maintained at 8.00–9.00 m under different unit loads. The research results can provide significant guidance for the operation optimization and fine management of the desulfurization system of the same type.