Preferential flow and soil strength degradation induced by desiccation cracks are important causes for expansive clay slope instability. The cyclic opening and closing of desiccation cracks during drying-wetting processes incessantly alters preferential flow paths and soil strength. Quantify the impact of desiccation crack dynamics on slope hydrology and stability remains a major unresolved challenge. To bridge this gap, we developed the first slope-scale hydro-mechanical model that couples weather-driven crack evolution with preferential flow while incorporating the deterioration effect on soil strength. This unified approach is a major contribution to our capacity to model the integration of hydrological processes and mechanical degradation of soil strength induced by dynamic cracks. The hydrological part adopted a dynamic dual-permeability model (dynamic DPM) and was validated by a physical slope model test. The dynamic DPM was then integrated into a set of numerical slope stability analyses under one-year atmospheric conditions. The groundwater level, water balance, pore water distribution, crack evolution and slope stability were investigated in the case of dynamic cracks and fixed cracks. The hydrological results showed that the slope model with dynamic cracks retained more water and higher groundwater level than that with fixed cracks. The narrowing of desiccation cracks slows down slope drainage process, resulting in a rapid build-up of pore water pressure due to preferential flow, which emerges as an often overlooked and significant factor contributing to slope instability. Conversely, fixed and well-connected cracks in soils enhance water drainage and thus benefit slope stability. The mechanical results revealed that the irreversible deterioration effect induced by crack dynamics on soil strength persistently degrades long-term slope stability. These findings provide new insights into failure mechanisms in cracked soil slopes, and show the importance of the integration of dynamic crack properties into climate-resilient slope design. Also, our results underscore the importance of understanding and quantifying the physical behavior of soil structures for soil hydrological response and slope stability assessment.