The Cobequid Highlands in Nova Scotia comprise a series of 365–360 Ma, REE-enriched, A-type granite plutons emplaced along an active shear zone. The purpose of this paper is to identify the sequence of REE minerals produced during long-lived, regional, hydrothermal circulation and its evolution through time. The fractures hosted in these granites were investigated using petrographic and scanning electron microscopes and the electron microprobe. Epidote-rich, biotite-rich, chlorite-rich, and Fe-oxide-rich fracture fillings have been observed. Mineral analyses revealed a variety of REE minerals in the fractures, including hydroxylbastnäsite-(Ce), parisite-(Ce), synchysite-(Ce), cerianite, thorite, Nb-bearing minerals, hingganite-(Y), and chernovite-(Y). Cross-cutting relationships and mineral associations indicate that the REE minerals precipitated at different times and are associated with specific styles of hydrothermal alteration. Epidote was one of the earliest minerals to precipitate in the fractures, associated only with minor precipitation of thorite and hydroxylbastnäsite-(Ce) and removal of As from sedimentary rocks, under low temperatures and reducing conditions. Biotite and chlorite precipitated shortly after epidote under more oxidizing conditions during which comparatively larger amounts of hydroxylbastnäsite-(Ce), thorite, hingganite-(Y), and cerianite formed. The Fe-oxide-filled fractures formed in the latest stages of hydrothermal circulation and are associated with the largest variety and highest amounts of hydrothermal REE minerals, such as parisite-(Ce), synchysite-(Y), thorite, Nb-bearing minerals, and chernovite-(Y). The oxidizing conditions led to the precipitation of As and the formation of chernovite-(Y) after the alteration of hingganite-(Y). Thus the greatest remobilization and concentration of REE minerals took place during late, high-temperature, oxidizing hydrothermal circulation, apparently driven by minor late mafic intrusions.