An efficient zinc(II)‐catalyzed alkyne oxidation/CH functionalization sequence was developed, thus leading to highly site‐selective synthesis of a variety of isoquinolones and β‐carbolines. Importantly, in contrast to the well‐established gold‐catalyzed intermolecular alkyne oxidation, over‐oxidation can be completely suppressed in this system and the reaction most likely proceeds by a Friedel–Crafts‐type pathway. Mechanistic studies and theoretical calculations are described. Swap gold for zinc: The title reaction was achieved by a zinc(II)‐catalyzed alkyne oxidation/CH functionalization sequence. In contrast to the well‐established gold‐catalyzed intermolecular alkyne oxidation, the over‐oxidation can be suppressed in this system and the reaction most likely proceeds by a Friedel–Crafts‐type pathway. Tf=trifluoromethanesulfonyl, PG=protecting group.