Context Lithology plays a crucial role in soil formation processes, and its interaction with soil properties is closely tied to climatic factors, making regional-scale investigations essential. Aims This study aimed to investigate the impact of lithology on both clay mineralogy and the physicochemical properties of soils in the O’Higgins region of central Chile. Methods We examined soils derived from seven distinct rock types: (1) lithic tuff (volcanoclastic, felsic); (2) andesite (volcanic, intermediate); (3) ash tuff (volcanoclastic, felsic); (4) breccia flow (volcanoclastic, intermediate; (5) granite (plutonic, felsic); (6) quartz schist (metamorphic); and (7) muscovite schist (metamorphic). A total of 21 topsoil samples (0–10 cm) and seven rock samples were collected for analysis. Key results Kaolinite and illite were ubiquitous in all soil samples, whereas smectite and vermiculite were restricted to soils derived from volcanic and volcanoclastic parent materials. Notably, the physicochemical characteristics of the soils converged toward a sandy loam texture with high base saturation levels (>90%). Conclusions The parent material exerts a significant influence on the clay mineral composition of soils in the study area. Conversely, the underlying lithology appears to have a negligible impact on the physicochemical properties of the soils in the region. Implications The findings of this study highlight the need for a more extensive and diverse sampling strategy to elucidate the complex relationships between lithology, soil clay mineralogy, and soil physicochemical properties. A more comprehensive understanding of these interactions can only be achieved through the inclusion of a larger and more representative sample set.