A divergent strategy is presented for the synthesis of 1,3-di- and 1,3,4-trisubstituted β-carbolines through an unprecedented one-pot triple-orthogonal-metal relay catalysis, and 1,3-disubstituted 4-hydroxy-β-carbolines through a one-pot bimetallic relay catalysis from readily accessible 3-(2-aminophenyl)-5-hexenyn-3-ols. These strategies were elaborated to enable the synthesis of benzofuro[2,3-c]pyridines, benzothieno[2,3-c]pyridines, and isoquinolines, which otherwise require multistep synthesis.