A long-sought-after reactive monophosphine-ligated palladium(0) intermediate, (PdL)-L-0 (L = phosphine ligand), was detected for the first time from the activation of the Buchwald precatalyst with base. The detection was enabled using desorption electrospray ionization mass spectrometry (DESI-MS) in combination with online reaction monitoring. The subsequent oxidative addition of (PdL)-L-0 with aryl halide and C-N coupling with amine via reductive elimination was also probed using DESI-MS.