Mineral grade estimation is a vital phase in mine planning and design, as well as in the mining project’s economic assessment. In mining, commonly accepted methods of ore grade estimation include geometrical approaches and geostatistical techniques such as kriging, which effectively capture the spatial grade variation within a deposit. The application of machine-learning (ML) techniques has been explored in the estimation of mineral resources, where complex correlations need to be captured. In this paper, the authors developed four machine-learning regression models, i.e., support vector regression (SVR), random forest regression (RFR), k-nearest neighbour (KNN) regression, and extreme gradient boost (XGBoost) regression, using a geological database to predict the grade in an Indian iron ore deposit. When compared with ordinary kriging (R² = 0.74; RMSE = 2.09), the RFR (R² = 0.74; RMSE = 2.06), XGBoost (R² = 0.73; RMSE = 2.12), and KNN (R² = 0.73; RMSE = 2.11) regression models produced similar results. The block model predictions generated using the RFR, XGBoost, and KNN models show comparable accuracy and spatial trends to those of ordinary kriging, whereas SVR was identified as less effective. When integrated with geological methods, these models demonstrate significant potential for enhancing and optimizing mine planning and design processes in similar iron ore deposits.