The catalytic cross-coupling of arylboronic acids with pyridines through single-electron oxidation provides efficient access to substituted heterocycles. Despite the importance of this reaction, very little is known about its mechanism, and as a consequence, it is unclear whether the full scope of the transformation has been realized. Here we present kinetic and spectroscopic evidence showing a high degree of complexity in the reaction system. The mechanism derived from these studies shows the activation of Ag(I) for reduction of persulfate and an off-cycle protodeboronation by the pyridine substrate. These results provide key mechanistic insights that enable control of the off-cycle process, thus providing higher efficiency and yield.