A gas-phase high-throughput reaction screening platform was developed for the first time to study chemical structures of closely related functional groups and for the discovery of novel organic reaction pathways. Experiments were performed using the contained atmospheric pressure chemical ionization (APCI) source that enabled nonthermal, nonequilibrium plasma chemistry to be monitored by mass spectrometry (MS) in real time. This contained-APCI MS platform allowed an array of reagents to be tested, resulting in the studies of multiple gas-phase reactions in parallel. By exposing headspace vapor of the selected reagents to corona discharge, solvent-free Borsche-Drecsel cyclization reaction, Katritzky chemistry, and Paal-Knorr pyrrole synthesis were examined in the gas phase, outside the high vacuum environment of the mass spectrometer. A new radical-mediated hydrazine coupling reaction was also discovered, which provided a selective pathway to synthesize secondary amines without using a catalyst. The mechanisms of these atmospheric pressure gas-phase reactions were explored through the direct capture of intermediates and via comparison with the corresponding bulk solution and droplet-phase reactions.