The Mt Isa-McArthur region is renowned for a range of commodities and deposit types of world-class proportions. The region is described here in the context of a mineral system, through consideration of processes that operate across a range of scales, from geodynamics and crustal architecture, to fluid sources, pathways, drivers and depositional processes. The objective is to improve targeting of Pb-Zn, Cu and Cu-Au deposits. Repeated extension and high heat flow characterise much of the history prior to 1640 Ma. The pre-Barramundi Orogeny (pre-1.87 Ga) metamorphic basement was the substrate on which a volcanic arc developed, focussed along the Kalkadoon-Leichhardt Belt. This is related to an inferred east-directed subduction between 1870 and 1850 Ma. From 1755 to 1640 Ma, three successive volcano-sedimentary basins developed, the Leichhardt, Calvert and Isa Superbasins, in an interpreted distal back-arc environment. The Isan Orogeny, from 1640 to 1490 Ma, overlapped with Isa Superbasin sedimentation, suggesting a transition from back-arc to a foreland basin setting. Most crustal thickening occurred in the Eastern Fold Belt, an area earlier characterised by thinned crust and deep marine environments. This region was deformed into nappe-like structures with high-temperature-low-pressure regional metamorphism and associated granites; the latter are absent from the Western Fold Belt. Metal deposition mainly occurred late in the history, with all known (and preserved) major base metal occurrences either hosted by Isa Superbasin rocks or formed during the Isan Orogeny.