Human pigmentation is a highly diverse and complex trait among populations, and has drawn particular attention from both academic and non-academic investigators for thousands of years. Previous studies detected selection signals in several human pigmentation genes, but few studies have integrated contribution from multiple genes to the evolution of human pigmentation. Moreover, none has quantified selective pressures on human pigmentation over epochs and between populations. Here, we dissect dynamics and differences of selective pressures during different periods and between distinct populations with new approaches. We propose a new model with multiple populations to estimate historical selective pressures by summarizing selective pressures on multiple genes. We use genotype data of 19 genes associated with human pigmentation from 17 datasets, and obtain data for 2346 individuals of six representative population groups from worldwide. Our results quantify selective pressures on light pigmentation not only in modern Europeans (0.0249/generation) but also in proto-Eurasians (0.00665/generation). Our results also support several derived alleles associated with human dark pigmentation may under directional selection by quantifying differences of selective pressures between populations. Our study provides a first attempt to quantitatively investigate the dynamics of selective pressures during different time periods in the evolution of human pigmentation, and may facilitate studies of the evolution of other complex traits.Author Summary The color variation of human skin, hair, and eye is affected by multiple genes with different roles. This diversity may be shaped by natural selection and adapted for ultraviolet radiation in different environments around the world. As human populations migrated out from Africa, the ultraviolet radiation in the environment they encountered also changed. It is possible that the selective pressures on human pigmentation varied throughout human evolutionary history. In this study, we develop a new approach and estimate historical selective pressures on light pigmentation not only in modern Europeans but also in proto-Eurasians. To our best knowledge, this is the first study that quantifies selective pressures during different time periods in the evolution of human pigmentation. Besides, we provide statistical evidence to support several genes associated with human dark pigmentation may be favored by natural selection. Thus, natural selection may not only affect light pigmentation in Eurasians, but also influence dark pigmentation in Africans.