In recent years, the ecological safety issues of red mud tailings ponds have been frequent, with problems such as the seepage damage of anti-seepage materials at the bottom of tailings ponds, failure of anti-seepage systems, and leakage of pollutants. In order to deeply analyze the influence of red mud (RM) leachate on the microstructure of the modified red clay (RC) anti-seepage layer, this article explores the influence characteristics of strong alkaline RM leachate on the microstructure of a modified RC anti-seepage layer under actual working conditions through a combination of permeability tests and microscopic characterization. The results showed that as the RM leachate permeation time increased, varying changes occurred in the permeability coefficient of the modified RC with different FA contents, among which the permeability coefficient of the modified RC with an 8% FA content showed a significant decreasing trend, reaching 5.98 × 10−11 m/s after stabilization. After permeation, numerous small pores were generated in the modified clay; furthermore, the small particles of the FA-modified clay were significantly reduced compared to pure clay. As the permeation time increased, the 8% FA-modified RC showed a phenomenon of first increasing and then decreasing in specific surface area, with a small change from 27.71 m2/g to 27.52 m2/g, indicating that this sample had high stability and the specific surface area was not significantly affected by permeation. This is mainly caused by the influence of gelling materials produced by the pozzolanic reaction and activation effect upon FA addition. The soil structure became more compact at the microscopic level with increasing FA content, resulting in particle aggregation, increased specific surface area, and narrowed small-pore size distribution. After 60 days of permeation, the single-shoulder peak of the 8% FA-modified RC was still the lowest at about 0.30 dV/dr. Compared to other samples, the pore size was smaller and less affected by the leachate. Overall, the microstructure of the 8% FA-modified RC was less affected by the leachate. This study provides an explanatory basis for the macroscopic mechanical phenomena by analyzing the influence of microstructure. It further provides a reference for studying the selection of anti-seepage materials.