The accurate prediction of overpressure before drilling is important for hydrocarbon exploration. It is almost impossible to directly predict the multiple origin overpressures via the existing methods that are related to anomalous porosity in a deep fold-thrust belt. Considering the Kelasu thrust belt (KTB) as an example, the compacting and loading curves in the KTB at the maximum burial period were restored. The measurements of fluid pressure obtained from drill-stem tests carried out at depth were then used to calculate the vertical effective stress offset (ΔVES) away from the restored loading curve. The unknown ΔVES was then predicted using the quantitative relationship between ΔVES, the distance from the axial surface of the fold forelimb or the distance to the thrust fault cutoff (FDIST), and the erosion thickness (ΔH). Finally, the vertical effective stress and overpressure were predicted using the predicted ΔVES, overburden stress, and loading curve. We found that mudstones formed at different rates of deposition would have different loading curves, which is a piecewise function that alternates between convex and concave functions. The convex function is more suitable for describing the loading and compaction behavior of strata with limited porosity strata (<3.5%), whereas the loading and compaction behavior of the strata with more significant porosity (>3.5%) can be better expressed by the concave function. The ΔVES induced by tectonic compression, transfer, and exhumation was found to present an inverse relationship with the FDIST but showed a positive relationship with the ΔH. Compared to Eaton’s method, the method developed in this study produces more accurate results and is, therefore, more appropriate for predicting the overpressure of intense tectonic compression, faulting, and exhumation fields in deep fold-thrust belts.