The Sanqiliu uranium deposit belongs to a uranium ore system in Motianling district. It is the oldest uranium deposit in South China. Primary uranium mineralization occurred almost simultaneously with the emplacement of the host granites and subsequent dykes, and it has a relatively high grade of uranium (0.421%). We clarify the age of mineralization and investigate the cooling history through new pitchblende U–Pb and apatite fission-track thermochronology. The pitchblende U–Pb results indicate that uranium mineralization occurred at ~801–759 Ma. Fractionation of uranium and lead at ~374–295 Ma is interpreted as remobilization and resetting of the original uranium. The Motianling area has apatite fission-track ages of 57 to 18 Ma. By combining our results with previous work, we conclude that the deposit cooled slowly and was exposed at the surface during the Cenozoic. The timing and depth of exhumation helped to preserve and avoid erosion of the uranium deposit, and highlight the potential for regional uranium exploration.