Copper homeostasis in bacteria is challenged by periodic elevation of copper levels in the environment, arising from both natural sources and human inputs. Several mechanisms have evolved to efflux copper from bacterial cells, including the cus and pco systems. The genes belonging to these two systems can be physically clustered in a Copper Homeostasis and Silver Resistance Island (CHASRI) on both plasmids and chromosomes in Enterobacteria. Increasing use of copper in agricultural and industrial applications raises questions about the role of human activity in the evolution of novel copper resistance mechanisms. Here we present evidence that CHASRI emerged and diversified in response to copper deposition across aerobic and anaerobic environments. An analysis of diversification rates and a molecular clock model suggest that CHASRI experienced repeated episodes of elevated diversification that could correspond to peaks in human copper production. Phylogenetic analyses suggest CHASRI originated in a relative of Enterobacter cloacae as the ultimate product of sequential assembly of several pre-existing two-gene modules. Once assembled, CHASRI dispersed via horizontal gene transfer (HGT) within Enterobacteriaceae and also to certain members of Shewanellaceae, where the original pco module was replaced by a divergent pco homolog. Analyses of copper stress mitigation suggest CHASRI confers increased resistance aerobically, anaerobically, and during shifts between aerobic and anaerobic environments, which could explain its persistence in facultative anaerobes and emergent enteric pathogens.