Understanding changes in redox conditions in the Earth's geological record is fundamental to unravelling some of the major events of our planet's history, such as the Great Oxidation Event (G.O.E.), biological changes through time related to mass extinctions, or the formation of ore deposits for primordial metal resources. Rocks from uranium deposits are ideal candidates to examine the coupled isotopic fractionation of Tl, Mo and U, as they are fundamentally caused by redox processes, occur in a wide variety of geological settings throughout much of geological history (from about 3 Ga), and result from the interplay between fluids and rocks of variable redox states. Herein we measure delta 97Mo (-10.2 to +6.1 %o), epsilon 205Tl (- 9.5 to +5.0 epsilon-units), and delta 238U (-0.72 to 0.30 %o) for 34 samples from granite-related, intrusive, metamorphic, and Proterozoic unconformity related U deposits. Collectively, these results suggest: 1) in metamorphic and unconformity-related contexts, samples with decreasing epsilon 205Tl values also have decreasing delta 238U values, indicative of change in redox conditions, 2) epsilon 205Tl values in the sulfide-rich samples likely reflect the affinity of 205Tl for these minerals, 3) Tl undergoes significant isotopic fractionation during the reduction of U-bearing fluids to precipitate uraninite, and 4) Tl isotopes do not fractionate during secondary remobilization of elements within these systems, and thus retain a record of the conditions of formation, whereas Mo isotopes are heavily fractionated by secondary remobilization. We suggest that the study of U, Mo, and Tl isotopes in U-ore deposits conveys new information related to building blocks of life on Earth and shows great potential for the study of past oxygenation events, thus potentially allowing us to reconstruct the geological and chemical history of our planet.