In the Athabasca Basin Proterozoic sandstones unconformably overlie Archean and Aphebian rocks. Multiple fluid events, involving isotopically- and chemically-distinct fluids which have migrated laterally for considerable distances and along fault zones, have produced a paragenetically-identifiable assemblage of clay, silicate and oxide minerals in the basin and basement rocks. Altered sandstones and the underlying metasedimentary rocks proximal to fault zones host high-grade UNiCo unconformity-type uranium ore deposits and contain an alteration assemblage of highly crystalline 2M/3T illite, 1M kaolinite, clinochlore and sudoite, hematite, dravite and euhedral quartz. In the sandstones, δ 18O-values of coeval quartz-hematite, quartz-illite, quartz-dravite, illite-hematite and kaolinite-hematite, fluid inclusion temperatures in diagenetic quartz, and δD-values of 1M kaolinite, 2M/3T illite, dravite and in fluid inclusions in the quartz indicate formation from a basinal fluid that had δD-values of ∼ −60±10‰ and which underwent salinity, temperature and 18O increases from 5 to 34 wt% NaCl, 120° to 240°C, and −5 to +3‰, respectively, as a result of increasing burial depth and sustained water-rock interactions with the basinal sediments over substantial time periods. 18O 16O and D/H ratios of sudoite and clinochlore in meta-sedimentary basement rocks within the alteration haloes indicate formation from a basement-derived fluid with δ 18O- and δD-values of +4±4 and +30±10‰, respectively, that was isotopically distinct from the basinal fluids. δ 18O- and δD-values of late kaolinites in reactivated fault zones indicate formation mainly from low-temperature (50-25 °C) fluids having δ 18O- and δD-values of −16 and −130‰, respectively, similar to relatively modern meteoric waters in the area. Some kaolinites have δ 18O- and δD-values which suggest they formed from meteoric waters at mid-latitudes and have experienced varying degrees of oxygen and hydrogen isotope exchange with relatively modern meteoric waters. In the re-activated faults, illite, sudoite and dravite have δD-values that vary by 100‰ without concurrent changes to their δ 18O-values, indicating preferential hydrogen isotope exchange with relatively modern meteoric waters at low temperatures and under conditions of high integrated water/rock ratios. RbSr isochron and model ages of 1477±57 and 952 Ma, respectively, for the crystalline 2M/3T illites indicate the timing of the high-temperature basinal fluid events associated with fluid mixing. RbSr and KAr ages on illites with the lowest δD-values are as young as 300 Ma and indicate late-stage resetting of their radiogenic isotope systematics as a result of substantial interactions with relatively modern meteoric waters. The evolution of Sr isotopic compositions of fluids in the basin and basement rocks, as reflected by the 87Sr 86Sr ratios of chlorite, illite and dravite, indicates that mixing of two isotopically-distinct fluids in the vicinity of faults was the process by which uranium was precipitated, similar to that suggested by oxygen and hydrogen isotope systematics in the clays and silicate minerals. ϵ Nd ratios in the high-temperature diagenetic and hydrothermal clay and silicate minerals and the cogenetic uranium ores suggest they all have formed from similar fluids which have interacted substantially with the basin sediments. In general, the isotopic, chemical, microthermometric and petrologic data indicate that the Athabasca Basin has had a protracted fluid history comparable to that documented for more modern sedimentary basins. The data clearly show that the major sandstone aquifers have been affected by widespread lateral flow of diagenetic fluids over distances of hundreds of kilometers and also that these fluid migration paths have been modified by cross-formational fluid flow near active fault zones.