Genetic diversity is ultimately the product of mutations that arise in germ cells and early embryos. Accurate knowledge of mutation rates and their variation across the tree of life is essential for calibrating inferences of demographic history and natural selection. By analyzing rates and patterns of mutagenesis within pedigrees, human populations, and other species, we have learned that both the overall rate of mutation and its distribution across genomic contexts vary as a function of reproductive life history and variation in DNA repair genes, including the glyosylase MUTYH that protects the genome from oxidative stress. However, we have not yet identified the cause of most of the mutation spectrum divergence that we measure among families, populations, and species. By comparing the rates and spectra of mutations among species, we have measured that the sequence biases of germline mutagenesis appear to drift over time in a way that parallels the neutral drift of segregating genetic variation. We can estimate the proportion of this drift that is due to changes in reproductive life history by utilizing the spectral biases found in human families with different reproductive life histories, and we find that this reproductive life history model is only able to explain a subset of the mutation spectrum variation that we measure over short and long evolutionary timescales.