This study investigated cryptic alteration haloes associated with copper mineralisation at Mount Isa, Northwest Queensland, Australia. New insights from hydrothermal alteration were used to constrain aspects of hydrothermal fluid flow and fluid-rock interactions that occurred as part of the mineralising system responsible for forming this world-class orebody. This study demonstrates the utility of several different approaches to identify and map cryptic alteration haloes associated with copper mineralisation at Mount Isa. Bulk geochemical techniques, such as carbon and oxygen stable isotope analysis and four-acid digest ICP-AES/MS analysis of assay pulps represent methods that can be readily applied during exploration to gain representative information about the mineralising system. Portable X-Ray Fluorescence (pXRF) represents a tool that can be used in a more targeted approach during exploration activities. With rigorous quality assurance and control procedures, pXRF can quickly and cost-effectively collect large datasets to identify broad trends across mineralising systems while minimising issues arising from sample heterogeneity at the scale of analysis. Integration of observations from previous studies and exploration data, with newly acquired petrographic and geochemical data collected across a range of scales, identified an extensive zoned alteration system that manifests as a series of interpreted reaction fronts, which extend at least 1500 m beyond mineralisation. Copper mineralisation is contained within a zone of visible mineral alteration, hydrothermal brecciation, and veining, locally known as the ‘silica-dolomite’. The silica-dolomite is characterised by silicification and brecciation of shales, recrystallisation of dolomite, and intense ¹⁸O-depletion, from δ¹⁸O ≈ 22‰ VSMOW in the least altered rocks to δ¹⁸O ≈ 10‰ in the most altered zone. These zones are spatially associated with structural dislocations on the contact between the Eastern Creek Volcanics and overlying metasediments of the Mount Isa Group that host copper mineralisation. These dislocations are interpreted to represent the fluid input zones to the mineralising system. A cryptic halo of K- and Ca-depletion extends from the inferred fluid input zones to include the region outboard of the visible mineral alteration envelope. This element depletion is interpreted to result from chloritisation and talc formation during silicification of white mica- and dolomite-bearing shale. Beyond the region of Ca-depletion and K-depletion, a large halo of cryptic potassic alteration is identified by whole-rock geochemical analysis. Potassium responsible for this alteration is interpreted to have been remobilised from zones of silicification and K-depletion at the core of the hydrothermal system. Although the ultimate sink of calcium mobilised from this core zone of element depletion remains unclear, a spatially extensive network of ore stage quartz-dolomite-calcite-pyrite veins has been documented. The change from dolomite- to calcite-dominated vein cement within individual veins is interpreted to be driven by increases in the relative activity of calcium during the evolution of the hydrothermal fluid as it moved away from the fluid input zone. Consequently, ore-stage veins with mixed dolomite-calcite vein cement potentially represent a distal expression of silicification and decalcification within the core of the mineralising system. The alteration haloes described above, both visible and cryptic, are all contained with the broad zone of ¹⁸O-depletion, representing the most spatially extensive alteration halo to copper mineralisation at Mount Isa. Copper mineralisation and associated hydrothermal alteration at Mount Isa developed due to fluid-rock interaction between ¹⁸O-depleted, low pH, silica-rich, cupriferous hydrothermal brines and variably carbonaceous and pyritic, carbonate-rich metasediments. Fluid flow responsible for developing the zoned hydrothermal alteration system was predominantly upward-directed and focused by structurally controlled permeability pathways. This fluid flow was sufficiently slow and warm enough to allow only moderate oxygen isotope disequilibrium between rock and the infiltrating hydrothermal fluids. In hydrothermal systems where fluids are undersaturated in metals, the size of the ore deposit will be limited by the time-integrated fluid flux. Not only can large hydrothermal systems with high time-integrated fluid fluxes form large ore deposits, but they will also be associated with large alteration haloes with greater distance between reaction fronts than smaller hydrothermal systems. Consequently, the zoned alteration system presented in this study assists in vectoring towards fluid input zones. At the same time, the spatial extent and spacing between reaction fronts provide an indicator of the prospectivity of the mineralising system at relatively early stages of exploration.