Long- term chemical weathering rate (LCWR) and chemical depletion fraction (CDF) are important parameters to characterize the degree of regional chemical weathering and reveal the evolution of landforms and climate. On a global scale, studies of long- term chemical weathering in mid- latitude areas are far more controversial than those in low- latitude areas. One of the reasons is that there is still uncertainty in theoretical understanding of their weathering mechanisms, especially the relationship between long- term chemical weathering and physical erosion, structure and climate in orogenic belt areas. In this paper, the geochemical mass balance method is used to systematically sort out and reanalyze the relevant data and materials for the typical mid- latitude orogenic belts in the northern hemisphere (the Heihe River basin in Central Asia and the Sierra Nevada in North America), estimate and compare their LCWR and physical erosion rate (E) values. The results show that the LCWRs of the Heihe River basin and Sierra Nevada are 17. 4~895 t/km2/a and 1~173 t/km2/a, respectively, and the CDFs are 0. 17~0. 81 and 0. 02~0. 61, respectively. LCWR is positively correlated with E, and only partially correlated with altitude, average annual temperature and average annual precipitation. The long- term chemical weathering in the study area is mainly characterized by “supply- limited” weathering, but some areas in the Heihe River basin have been in the transitional stage of “supply- limited” and “kinetically- limited”. Combined with the results of regression analysis and the comprehensive analysis of existing data, it is found that the long- term chemical weathering rate in mid- latitude orogenic belt is influenced by geological and climatic factors, but the main controlling factor is geological, while the chemical depletion fraction is mainly controlled by other factors.