Guilin is a famous karst area, and currently the view that the disintegration of red clay will cause soil cave collapse is increasingly recognized. In order to study the influence of the coupling effect of moisture content and void ratio on the disintegration of red clay, different moisture contents and void ratios of Guilin red clay were placed on a self-made disintegration apparatus to record the real-time disintegration amount and observe the disintegration phenomenon. Images of the structural characteristics of soil were obtained by a scanning electron microscope (SEM). Additionally, nuclear magnetic resonance (NMR) was applied to analyze the distribution of water in both natural and saturated states. The results show that the disintegration rate of red clay decreases as the initial moisture content increases, but increases with the increase of void ratio. Both moisture content and void ratio affect the structural characteristics of red clay. When the moisture content remains constant, the soil changes from a three-peak to a two-peak structure as the void ratio increases. The total area and secondary peak area of the T2 spectrum increase, while the starting T2 value of the main peak shifts to the right and the area decreases. Meanwhile, the starting T2 value of the secondary peak shifts to the right and the area increases. When the void ratio remains constant, the starting T2 value of the main peak gradually shifts to the left and the area decreases as the moisture content increases. However, the starting T2 value of the secondary peak shifts to the right and the area decreases or first decreases and then increases. The disintegration rate does not exhibit a significant relationship with either pore volume or macropore volume. The combined water saturation shows a bilinear relationship with both the moisture content and void ratio, where it increases as the initial moisture content increases, but decreases as the void ratio increases, with a correlation coefficient of 0.9929. The disintegration rate has an exponential relationship with the combined water saturation, and it decreases as the combined water saturation increases, with a correlation coefficient of 0.9934.