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High rates of limestone have been increasingly utilized in newly converted areas for grain production in agricultural frontier regions to expedite the short-term correction of soil fertility, leading to compensatory yields. However, there is a lack of information about different doses of lime and gypsum for soils in the Cerrado of Matopiba, especially in the state of Piauí, Brazil. The aim of this study was to evaluate the effects of doses of lime and gypsum in newly converted areas for soybean production in the Cerrado of Southwest Piauí. The study was carried out in the 2019/2020 and 2020/2021 crop years, on yellow Oxisol soil, in a randomized block design and treatments following a 5 × 4 factorial: five lime rates (0, 5, 10, 15, and 20 t ha−1) and four gypsum rates (0, 1, 2 and 4 t ha−1), with four replicates. The standard lime and gypsum rates were 5 t ha−1 and 1 t ha−1, respectively. Soil fertility attributes (0.0–0.2, 0.2–0.4, and 0.4–0.6 m), nutritional status of plants, and soybean yield were measured. The increases in grain yield using a lime rate of 10 t ha−1 were 18% and 12% in the 2019/2020 and 2020/2021 crop years, respectively. High lime rates provide a reduction in the concentrations of P, K, and cationic micronutrients in soil, thereby reducing leaf contents of macro- and micronutrients in soybean plants. Concentrations of Ca, Mg, and S in subsurface layers were raised to proper levels, similar to those recommended for topsoil (0.0–0.2 m). The use of gypsum and lime in newly converted areas for soybean cultivation provides quick improvement in soil chemical conditions and reduction in acidity components. The application of 10 t ha−1 of lime improved the soil chemical environment in the Matopiba region the short time available for chemical reactions to occur, allowing soybean cultivation in newly converted areas of Cerrado into agriculture.