Experimental results and computational insights explain the key role of transition-metal catalysis/Brønsted acid synergism in the achievement of the sequential regioselective direct heteroarylation/cyclocondensation reactions of β-(2-aminophenyl)-α,β-ynones with a variety of electron-rich aromatic heterocyclic/arenes to afford quinoline-(hetero)aromatic hybrids. The first approach to the synthesis of 4-(1H-pyrrol-2-yl)quinolines is described. The effectiveness of various transition metals is compared.