Life is powered by planet-wide disequilibria between reducing and oxidizing phases in the crust, ocean and atmosphere. Oxidoreductases (ORs) are critical enzymes that couple electron transfer to catalysis, allowing life to access this energy and generate building blocks of biomacromolecules. Modern ORs are sophisticated nano-machines that came from simple, now extinct ancestors. A structural bioinformatics approach is described probing the deep-time evolution of ORs. Proposed primordial ORs are designed computationally and studied in the laboratory. We find that the earliest electron carriers were likely simple and robust molecules with high evolutionary potential.