Visible-light-activated photocatalysis has emerged as a green and powerful tool for the synthesis of various organic compounds under mild conditions. However, the expeditious discovery of novel photocatalysts and synthetic pathways remains challenging. Here, we developed a bifunctional platform that enabled the high-throughput discovery and optimization of new photochemical reactions down to the picomole scale. This platform was designed based on a contactless nano-electrostatic-spray ionization technique, which allows synchronized photoreactions and high-throughput in situ mass spectrometric analysis with a near-100% duty cycle. Using this platform, we realized the rapid screening of photocatalytic reactions in ambient conditions with a high speed of less than 1.5 min/reaction using picomolar materials. The versatility was validated by multiple visible-light-induced photocatalytic reactions, especially the discovery of aerobic C-H thiolation with low-cost organic photocatalysts without any other additives. This study provided a new paradigm for the integration of ambient ionization techniques and new insights into photocatalytic reaction screening, which will have broad applications in the development of new visible-light-promoted reactions.