Mineralized shear zones in the Archean Missanabie-Renabie gold district (~ 1.1 Moz Au; Wawa, Ontario, Canada) locally define composite orebodies that record three hydrothermal events: (1) a pre-orogenic Au1 event (pre-D1 and pre-prograde-metamorphic); (2) a syn-orogenic, post-peak-metamorphic Retrograde event (syn-D3); and (3) a late syn-to post-orogenic Au2 event (late syn- to post-D4). Genetic considerations indicate the orebodies are hybrids with early intrusion-related (Au1) and later orogenic (Retrograde + Au2) events. Pearson product-moment correlation coefficients (log10) of whole-rock and LA-ICP-MS pyrite trace metal datasets distinguish Au1 from Au2 mineralization by Au-Ag, Au-Bi, and Au-Te correlations > 0.7 (p < 0.05) in the former, irrespective of sample medium and analytical method. An Au-Mo correlation in whole rock data (0.58–0.76; p < 0.05) further distinguishes Au1 from Au2 and supports an independently inferred intrusion-related origin for Au1. Sulfur isotope data is similar for both Au1 and Au2 pyrite with average δ34S values of − 5.5‰ ± 0.2‰ (1σ) and − 3.5‰ ± 0.3‰ (1σ) and average Δ33S values of 0.4‰ ± 0.1‰ (1σ) and − 0.3‰ ± 0.2‰ (1σ), respectively. SIMS δ18Oquartz values for the Au1, Retrograde, and Au2 events largely overlap and, like δ18Ocarbonate values of previous studies, tend to be lower than values typical of Archean gold deposits. The results of this study suggest that correlation coefficients in trace metal datasets are useful in discriminating and characterizing different gold events. Caution is emphasized with the use of S- and O-isotope datasets for these purposes. The presence of low δ18O values in vein quartz and carbonate is best explained by an 18O-depleted fluid formed during the Retrograde hydrothermal event. The latter is inferred at 2580 ± 21 Ma based on U-Pb geochronlogy of hydrothermal titanite, and relates to deformation and metamorphism in the nearby, amphibolite- to granulite-grade Kapuskasing metamorphic belt. Geochronological and geochemical evidence suggest that the 18O-depleted fluid may have formed via the devolatilization of biotite-bearing granitoids during deep-crustal metamorphism.