A screening method for the rapid identification of catalytic conditions for Pd-catalyzed C-N cross-coupling reactions is reported. The strategy evaluates mixtures of precatalysts, ligands, and bases to identify productive conditions that are subsequently optimized through two deconvolution steps, which uncover the active catalyst and identify the optimal solvent and base for the catalytic system. The efficacy of this approach was demonstrated through application to a previously reported reaction, whereby both the literature conditions and additional solutions were retrieved. The same approach to Ni-catalyzed C-N cross-coupling was investigated in parallel but was found to be less successful due to limited activity of the evaluated reagent combinations. Finally, the utility of this method was showcased by identifying effective conditions for the Pd-catalyzed cross-coupling of complex molecules, which not only revealed nonobvious solutions for the processes under evaluation but also resulted in the discovery of new chemical reactions.