Little is known about differences in germline mutation processes between extant mammals. We analysed genome sequences of mouse and human pedigrees to investigate mutational differences between these species. We found that while the generational mutation rate in mice is 40% of that in humans, the annual mutation rate is 16 times higher, and the mutation rate per cell division is two-fold higher. We classified mutations into four temporal strata reflecting the timing of the mutation within the lineage from zygote to gamete. The earliest embryonic cell divisions are the most mutagenic in both species, but these earliest mutations account for a much higher proportion of all mutations in mice (~25%) than in humans (~5%). We observed a strong sex bias in the number of mutations arising in subsequent cell divisions in the early embryo in mice, but not in humans. Finally, we reconstructed partial genealogies of murine parental gametes that suggest markedly unequal contributions from founding primordial germ cells.