Low-permeability clays are characterized by a large amount of clay minerals and a special distribution of pore sizes, so their seepage behavior shows an obvious pore size effect. Therefore, conventional seepage theories show deviations in describing the seepage behavior of low-permeability clays. This paper analyzes two reasons for the pore size effect in low-permeability clay seepage: the pore distribution property and the electric double layer effect of the clay surface. Considering these two factors, the seepage theory of the pore size effect based on the microscale seepage of the circular tube model is proposed. The rationality of this theory is tested by the seepage experiments of natural undisturbed clay and artificial clay, and from these experiments, three beneficial conclusions are drawn: (1) The results of the pore size effect seepage theory are in good agreement with the experimental results and are better than the modified Kozeny-Carman equation; (2) The properties of the electric double layer have a certain regular influence on the seepage behavior of the clay; (3) Considering the properties of the soil pore size distribution, the results obtained by using the pore size effect theory are much closer to the experimental results than the results calculated using the average pore diameter of the clay.