The Ernest Henry Iron-Oxide-Copper-Gold deposit is the largest known Cu-Au deposit in the Eastern Succession of the Proterozoic Mount Isa Inlier, NW Queensland. Cu-Au mineralization is hosted in a K-feldspar altered breccia, bounded by two major pre-mineralization shear zones. Previous research suggests that Cu-Au mineralization and the ore-bearing breccia formed simultaneously through an eruption style explosive/implosive event, facilitated by the mixing of fluids at ~1530 Ma. However, the preservation of a highly deformed, weakly mineralized, pre-mineralization feature (termed the Inter-lens) within the orebody indicates that this model must be re-examined. The paragenesis of the Inter-lens is broadly consistent with previous studies on the deposit, and consists of albitization; an apatite-calcite-quartz-garnet assemblage; biotite-magnetite ± garnet alteration; K-feldspar ± hornblende alteration; Cu-Au mineralization and post-mineralization alteration and veining. Apatite from the paragenetically early apatite-calcite-quartz-garnet assemblage produce U–Pb ages of 1584 ± 22 Ma and 1587 ± 22 Ma, suggesting that the formation of apatite, and the maximum age of the Inter-lens is synchronous with D2 deformation of the Isan Orogeny and regional peak-metamorphic conditions. Apatite rare earth element-depletion trends display: (1) a depletion in rare earth elements evenly, corresponding with an enrichment in arsenic and (2) a selective light rare earth element depletion. Exposure to an acidic NaCl and/or CaCl2-rich sedimentary-derived fluid is responsible for the selective light rare earth element-depletion trend, while the exposure to a neutral to alkaline S, Na-, and/or Ca-rich magmatic fluid resulted in the depletion of rare earth elements in apatite evenly, while producing an enrichment in arsenic. We suggest the deposit experienced at least two hydrothermal events, with the first event related to peak-metamorphism (~1585 Ma) and a subsequent event related to the emplacement of the nearby (~1530 Ma) Williams–Naraku Batholiths. Brecciation resulted from competency contrasts between ductile metasedimentary rocks of the Inter-lens and surrounding shear zones against the brittle metavolcanic rocks that comprise the ore-bearing breccia, providing permeable pathways for the subsequent ore-bearing fluids.