Arsenic is a ubiquitous metalloid in the biosphere and notorious for its toxic properties. The universal toxicity of arsenic is depicted by the presence of resistance genes in the genomes of most living things spread across the three domains of life. Moreover, the expression of arsenic resistance genes in primitive prokaryotes near the base of the tree of life and in more recently evolved complex eukaryotes, suggest arsenic toxicity ancient and that it continues to play a crucial role in the organisation of the modern biosphere. Here, it is demonstrated that the concentration and redox behaviour of arsenic in seawater has varied dramatically through Earth history, controlled by climate, weathering fluxes from the continent and atmospheric oxygen content. The data show that it was not until 2450 million years ago that arsenate and arsenic sulfides rose to global prominence in seawater, coincident with the first permanent rise of oxygen in the atmosphere. It is proposed that it was at this time that the modern arsenic cycle was first established globally, triggering the onset of severe arsenate toxicity and competition with phosphate for uptake into cells.