This work aimed to evaluate the impact of conversion from native vegetation to pastures and agriculture on soil quality in the Brazilian semi-arid region and identify which soil attributes have the greatest potential as soil quality indicators. We collected soil samples at 0–10 and 10–20 cm layers from seven municipalities in the Brazilian semi-arid region. We determined the stocks of total soil organic carbon (TOC), total nitrogen (TN), carbon and nitrogen from microbial biomass (MB-C, MB-N), oxidizable fractions, humic substances, granulometry, soil bulk density (BD), pH, P, and cation exchange capacity (CEC). The evaluated systems were pasture, agriculture with different implementation times, and native forest (Caatinga biome). The results show that conventional cultivation and grazing systems lead to substantial losses of fundamental attributes needed to maintain soil quality. The study observed losses of MB-C, TOC, TN, and more recalcitrant fractions like fulvic acid and humin, along with a reduction in soil P and CEC. Soil physical, chemical, and biological attributes work as indicators of separation between environments; however, labile compartments showed greater potential as indicators of land use changes, being considered the main indicators in the soil quality assessment.