Thermal convection and fluid mixing are involved in the formation of many mineral deposits, but their relationships and roles in mineralization remain poorly understood because they are generally investigated separately in different studies. Here we present a case study combining thermal convection and fluid mixing to examine the critical factors that controlled the formation of high-grade, world-class unconformity-related uranium (URU) deposits in the Athabasca Basin (Canada). Reactive transport modeling of various scenarios with different degrees of involvement of thermal convection and fluid mixing shows that significant URU mineralization occurs at the intersection of a basement fault with the basin-basement unconformity only if thermal convection and basin-basement fluid mixing take place concurrently. If there is no thermal convection in the basin, only sparse U mineralization occurs along the unconformity. If insufficient amount of reducing fluid is provided from the basement along the fault, no significant U mineralization occurs either. Furthermore, no significant U mineralization occurs if the U concentration in the basinal fluid is low. We conclude that the exceptionally rich U endowment in the Athabasca Basin is the result of coupling of three critical factors: highpermeability sandstone favoring thermal convection in the basin, ample supply of reducing agents by basement fluids along reactivated basement faults, and abundant U-rich basinal fluid available in the basin sequences. Similar coupling of fluid processes may be essential for the formation of other types of mineral deposits.