Evaluation of soil sustainability should take into account chemical and mineralogical changes due to cultivation. Potassium (K) application is a key farming practice that may potentially affect phyllosilicate composition and soil properties. Irrigation is another agent that affects soil composition. This study aims to evaluate the imprints of cultivation on the chemical and mineralogical compositions of lowland soils under semi-arid and Mediterranean climate regimes and to assess them with the natural pedogenesis. The sites examined include two permanent plot experiments with crop rotation, and three single-plant plots. Cultivated, control, and fallow soils were analyzed for their chemical and mineralogical composition. The X-ray diffraction patterns of the clay fraction were decomposed to achieve quantitative detection of changes among the illite–smectite (IS) phases and in kaolinite amounts. In loamy and clayey soils dominated by IS phases, cultivation caused minor changes and diverse behavior of the IS phases. Yet, the K balance was negative under high fertilization levels and higher plant mass production. Fertilization enhanced the natural process of transforming IS into kaolinite and illite in the sandy soil, leading to a positive K balance. This study emphasizes the importance of IS minerals as a dynamic K pool that responds to plant needs.