To observe authentic biological processes in living cells, it is critical to avoid damaging or perturbing them. Fluorescence microscopy suffers from the need to illuminate biological samples with extremely bright light to collect sufficient signal. A majority of this incident light is not absorbed by the fluorophores being imaged and is a source of collateral damage to many other components of the cell. Bioluminescent proteins, luciferases, produce light via enzymatic oxidation of a small molecule substrate, a luciferin. These substrates, such as coelenterazine, are essentially biologically inert in cells, and because the light they produce does not require exogenous excitation, imaging with bioluminescent probes does not lead to phototoxicity or other undesirable perturbations. In theory, bioluminescence is ideal for live cell imaging. Unfortunately, all of the available bioluminescent probes are too dim for use in most imaging experiments. Increasing the photon output is difficult because luciferases are fundamentally limited by the need to balance catalytic rate and luminescence quantum yield. In other words, to achieve a high quantum yield, the luciferase must stabilize the excited oxyluciferin in a protected binding pocket that discourages non-radiative relaxation to the ground state. This requirement places major constraint on the dissociation constant of the ground state oxidized substrate, slowing down substrate turnover and reducing the number of photons emitted per second. Here, we use a novel approach leveraging Förster resonance energy transfer (FRET) to eliminate this trade off. First, we optimize FRET efficiency between our highest-activity luciferases and our brightest fluorescent protein variants to increase total light output. We then use structure-guided design and directed evolution to improve the turnover number of the luciferase component. This combination design process circumvents the critical ‘catalytic rate versus quantum yield' barrier, giving way to the next generation of bright bioluminescent light sources.