Abstract Times of metal-rich brine discharge into ancient ocean basins, associated with the formation of sedimentary-exhalative (sedex) Zn-Pb-Ba ore deposits, coincided with short-duration positive excursions (“spikes”) in the global marine Sr isotope record. While these spikes are unexplained by conventional oceanic models, chronostratigraphic correlations, combined with mass balance evidence and oceanographic modeling, suggest that the flux of radiogenic Sr from sedex brines during ore formation is sufficient to explain these previously enigmatic 87 Sr/ 86 Sr spikes. We review existing 87 Sr/ 86 Sr data and present new data as verification of these global 87 Sr/ 86 Sr spikes and their correlations with the formation of giant sedex ore deposits. Major events include an 1 ×10 −4 (~0.7078–~0.7079) excursion contemporaneous with formation of the Rammelsberg deposit at ~389 Ma; spikes on the order of 1 to 3 × 10 −4 , coeval with formation of the Meggen deposit at ~381 Ma, several ore deposits in the Macmillan Pass district at ~379 to 375 Ma, and the Silvermines deposits at ~352 Ma; and two >6 × 10 −4 spikes coincident with formation of the giant Navan deposit at ~346 Ma and Red Dog deposits at ~337 Ma. Moreover, the timing of peak 87 Sr/ 86 Sr spikes correlates with global δ 13 C and δ 18 O spikes, deposition of metal-rich black shales and ironstones, metal-induced malformation (teratology) of marine organisms, and mass extinctions. The relationships among these features were poorly understood, but our new model explains how the flux of key biolimiting nutrients and metals contained in sedex brines, demonstrably equivalent to or exceeding that of the total modern riverine flux to the ocean, spurred ocean eutrophication, which, ultimately, through a series of positive feedback mechanisms, may have triggered global chemical and biological events. If, as we hypothesize, sedex hydrothermal systems are recorded in the global marine isotopic, geologic, and biological records, our findings define a new approach to the study of and exploration for sedex deposits. We demonstrate that fluid inclusion solute chemistry and isotopic and stratigraphic studies of sedex deposits, coupled with chronostratigraphic correlation and high-resolution 87 Sr/ 86 Sr isotope chemostratigraphy, can be used to answer long-standing questions about geologic processes responsible for formation of these extraordinary deposits. This approach provides evidence for the age, duration, and fluxes of fluids and metals vented into the ocean by these giant hydrothermal systems. Accordingly, the marine 87 Sr/ 86 Sr curve constitutes a global exploration tool that could be applied to assess the mineral potential of sedimentary basins. To illustrate the potential of this tool to identify favorable stratigraphic ages and basins with potential for undiscovered giant sedex deposits, we highlight several spikes, on par with those characteristic of the Red Dog and Navan deposits, which have not been correlated with known metal deposits. Given these strong temporal correlations, mass balance estimates, and results of ocean chemistry modeling, our study suggests that further work is warranted to determine the extent to which periodic venting of hydrothermal basinal brines into the ocean has influenced the evolution of marine chemistry. Ultimately, these global signatures can be applied to the study of and exploration for sedex deposits.