A fundamental goal of neuroscience is to decipher the neural activities underlying behaviors in vivo. Among existing tools for neural recording, genetically encoded voltage indicators (GEVIs) — protein-based fluorescent indicators whose brightness is directly modulated by membrane potential — hold the most promise for large-scale measuring of neural activities with cell-type specificity, subcellular spatial resolution, and sub-millisecond temporal resolution. However, current GEVIs have limited utility in vivo due to their suboptimal performance, especially under two-photon microscopy (2PM), a desired method for deep-tissue imaging. To address these limitations, we started from building a high-throughput screening platform that can evaluate all key metrics of a GEVI under one-photon illumination. Directed evolution on this platform led to JEDI-1P, a green-emitting GEVI optimized for widefield voltage imaging. With improved brightness, kinetics, sensitivity and photostability, JEDI-1P empowered chronic pan-cortical voltage imaging and robust detection of rapid voltage signals in behaving mice. Next, we sought to optimize GEVI for deep tissue imaging by extending the screening platform with a two-photon resonant scanning system. Using this 2P screening platform, we identified JEDI-2P, whose brightness, sensitivity and photostability under 2PM were all significantly improved over its parental indicator. We showed that JEDI-2P can capture voltage responses to visual stimuli in the amacrine cells of isolated mouse retina and the axonal projections of Drosophila interneurons. With excellent 2P photostability, JEDI-2P enabled prolonged continuous recording from individual cortical neurons in awake behaving mice with both resonant-scanning 2PM and ULoVE random-access microscopy. In particular, we highlighted that the improved sensitivity and brightness of JEDI-2P allowed the first high-fidelity voltage recording from mice Layer 5 cortical neurons as well as robust recordings of pairwise voltage correlations during behavior. Taken together, JEDI-2P fills the vacancy of a GEVI optimized for 2P applications and paves the way for long-term studying of deep brain neural activities. Finally, to enable all-optical electrophysiology and multi-spectral imaging under two-photon microscopy, we designed a red-emitting voltage indicator from scratch. After rationally engineering the interface between the chromophore and the voltage-sensing domain, we identified VADER1, the first red-emitting GEVI that has demonstrated the capability to resolve single action potentials in mice under two-photon illumination. We anticipate the expanded GEVI toolbox will enable high-throughput and real-time recording of action potentials from the genetically specified group of neurons in live animals, thereby helping interpret the computation mechanism of neural circuits with unprecedented spatiotemporal resolution.