Orogenic gold deposits are unevenly distributed in geologic time. The richest period of orogenic gold deposit formation was the Phanerozoic, which followed a >1-b.y. period of relatively meager deposit generation during the Proterozoic. This Proterozoic low-gold period developed despite continent-building episodes, which should have been appropriate for orogenic gold genesis. Here, a brief review of the changes in global geochemistry brought on by evolving interactions between plate tectonics and the biosphere is conducted before the consequences for gold uptake into sedimentary pyrite are discussed. It is suggested that the extensive oxygenation of the deep oceans during the second Great Oxidation Event, over the period 635 to 510 Ma, produced conditions where gold was soluble in the deep oceans from that point on. Regions where bacterial sulfate reduction drove formation of sedimentary pyrite also destabilized this soluble gold, promoting its uptake into pyrite, and allowing formation of metallogenically enhanced sedimentary sequences. These sediments would have become ideal source rocks for gold deposits during subsequent collisional tectonics and metamorphism. This biogenic influence on source region enhancement may explain the association during the Phanerozoic eon between some of the world’s most gold productive regions and sedimentary sequences that contain pyritic carbonaceous rocks.