The complex structure of Neogene mudstone plays an important role in geological disasters. A close relationship exists between the mechanisms of mudstone landslides and the disintegration characteristics of rocks. Therefore, understanding the disintegration characteristics of Neogene mudstone at different depths is crucial for enhancing engineering safety and assessing landslide stability. This study employed Neogene mudstone from different depths to perform disintegration and plastic limit experiments and revealed the sliding mechanisms of landslides involving Neogene mudstone, providing theoretical support for mitigating mudstone geological disasters. Our results demonstrate that Neogene mudstone from different depths experiences varied stress conditions and pore water pressure due to geological actions, significantly affecting the disintegration characteristics. By ignoring the factors of the slip surface, the slake durability index of mudstone decreases with increasing burial depth, while the plasticity limit index tends to rise. The influence of groundwater, geo-stress, and pore structure on Neogene mudstones at different depths results in overall weak stability and disintegration. Landslide occurrences are likely connected to the mechanical properties of mudstones at the slip surface, where a low slake durability index and higher plasticity index make the mudstones prone to fracturing, breaking, and disintegrating once in contact with water.