The Middleback Ranges is a 60 km-long BIF-endowed iron ore belt located in the southeastern Gawler Craton and is the largest exploited iron resource in South Australia. The belt is hosted within an Archean- to Paleoproterozoic-aged granitic-gneissic basement terrane. Petrographic and geochronological constraints are given for a suite of granites associated with deposits throughout the Middleback Ranges and compared with other regional granites. Granites from the Middleback Ranges show complex mineralogical and geochemical features indicating multiple overprinting events. Sensitive high-resolution ion microprobe U-Pb zircon ages from all granites across the Middleback Ranges yield Archean ages, suggesting the existence and a more extensive distribution of Mesoarchean crust than previously recognized beneath the entire Middleback Ranges BIF sequence. Grey and pink granites from the central Middleback Ranges (Sultan prospect) produced the oldest 207Pb/206Pb weighted mean ages within the sample suite (3241 ± 6 and 3238 ± 9 Ma, respectively). Zircon in the latter granite also features overgrowths dated at ∼2.6 Ga and interpreted to be metamorphic. A second group of younger granites from the Iron Monarch deposit and a sample of Cooyerdoo Granite (northern Middleback Ranges) have a minimum crystallization age of 3165 ± 8 Ma and a 207Pb/206Pb weighted mean magmatic age of 3134 ± 18 Ma, respectively. The youngest granites analyzed here derive from the Iron Baron deposit in the central part of the belt, which display strong deformation and have a minimum crystallization age of 3089 ± 9 Ma, and from the Iron Magnet deposit in the southern part of the belt (207Pb/206Pb weighted mean age of 3023 ± 33 Ma). Petrographic and geochemical features observed within the sample suite indicate that post-Archean overprinting events led to alteration of the granitic basement and may infer that fluid-rock interaction and granite leaching were important for BIF upgrading processes and iron-oxide formation.