Soil–vegetation–atmosphere interaction has long been known to induce significant pore pressure variations at shallow depths and associated superficial slope movements. Recent findings suggest that the effect of this interaction may also extend to large depths in natural clay slopes. Multiple examples of weather-induced deep landslide mechanisms can be found in the Southern Apennines (Italy), where slopes are often formed of fissured clays. The relationship between the activity of these landslides and the hydro-mechanical processes due to soil–vegetation–atmosphere interaction was investigated herein by means of a two-dimensional coupled hydro-mechanical finite element analysis. A constitutive model capable of simulating the behaviour of highly overconsolidated clays, in both saturated and unsaturated states, was adopted in the analysis, in conjunction with a boundary condition capable of reproducing the combined effects of rainfall infiltration, evapo-transpiration, and run-off. The results of the analysis corroborate the connection between weather conditions, pore pressure variations, and slope movements in natural clay slopes. The importance of adequately reproducing the geological history of a natural slope to define its current state is also demonstrated.