Both background radiation levels and atmospheric oxygen concentrations have changed dramatically over the history of life on Earth. Oxygen has a strong modifying influence on radiogenic mutation rates. Therefore, background radiation levels and atmospheric oxygen concentrations must be considered jointly to determine changes in radiogenic mutation rates through geologic time. Using accepted models that describe how both of these parameters have changed through geologic time, we find that radiogenic mutation rates in organisms have likely fluctuated between about 1.5 to 2.5 times current levels through most of the history of life on Earth. Further, radiogenic DNA damage rates have likely decreased monotonically for most of the last 1 Ga, although DNA damage associated with increasing atmospheric oxygen levels have increased by a greater factor for organisms living in oxygenated environments. The results of this study have interesting implications that may impact our understanding of how modern organisms respond to radiation damage and of models that use molecular clocks to date deep divergence times of the major groupings of organisms. It is also possible that changing oxygen levels have served to buffer changes in DNA damage rate over time.