The Irtysh River is an international river partially joining the territories of China, Kazakhstan, and Russia. Cascade reservoirs have been constructed in the upper reaches of the river and their effects on the seasonal discharge of the middle and lower reaches were analyzed considering the mean and dispersion of the seasonal discharge. The Lepage test, which is a nonparametric, two-sample test for detecting location and dispersion, was used to measure the significance of difference between the pre-dam and post-dam seasonal discharge. The results show that the reservoirs’ effects on the seasonal discharge varied with the season. In the middle reaches of the river, the summer and autumn discharge decreased significantly and their inter-annual variabilities also decreased significantly. The summer and autumn precipitation over the Irtysh River Basin changed little before and after the operation of the reservoir, which indicates that the discharge changes mainly due to water storage of the reservoirs. The reservoirs store water in summer and autumn and store more water in a wet year, which leads to the reduction of the mean and dispersion of the summer and autumn discharge. The winter discharge increased significantly because the reservoirs released water for power generation. The spring discharge changed slightly. In the lower reaches, only the winter discharge increased significantly, and the other seasonal discharge changed slightly. The reservoirs’ effects on the seasonal discharge are more significant in the middle reaches than in the lower reaches.