The ecological and environmental security of the Kherlen River Basin has attracted more and more attention in China and Mongolia. It is of great significance to investigate the contents of soil total nitrogen (STN) and soil total phosphorus (STP) in the basin for accurately estimating the load of non-point sources (NPS) and studying the state of resources and environment and sustainable development. It is time-consuming and labor-intensive to obtain a wide range of STN and STP contents using traditional sampling methods, while STN and STP not only have spatial heterogeneity, but also have heterogeneity in their relationships with auxiliary variables. Moreover, a single global model cannot fit complex heterogeneous relationships, and it is difficult for the local modeling method to overcome dimensional disaster problems. Therefore, the two-point machine learning (TPML) method is introduced in this paper. The TPML method first establishes a global model based on the difference of paired points, and then constructs a local model based on the prediction difference of the global model. It can expand the sample size from n to n², achieving the prediction of high-precision and large-scale STN and STP contents using limited sampling points. Based on 18 auxiliary variables of topography, climate, soil properties, vegetation and spatial location, etc, the study produced the distribution dataset of STN and STP contents in the basin using the TPML method. Futhermore, using the ten-fold cross-validation method, the study confirmed that the prediction accuracy of TPML model is more than 10% higher than that of Ordinary Kriging (OK) model. The mean absolute deviation (MAE) and mean root mean squared error (RMSE) of STN content predicted by the TPML method are 0.309% and 0.456% respectively. The mean MAE of STN content predicted by random forest (RF), inverse distance weighted (IDW) and OK methods is 0.329%, 0.247% and 1.864%, and the mean RMSE is 0.468%, 0.387% and 1.976%, respectively. The mean MAE and mean RMSE of STP content predicted by TPML method are 0.640% and 0.861%. The mean MAE of STP content predicted by RF, IDW and OK methods is 0.643%, 0.396% and 1.357%, and the mean RMSE is 0.862%, 0.523% and 1.651%, respectively.