Annulations through dual C-H activation represent a powerful tool to selectively assemble multi-cyclic scaffolds. We present herein a palladium-catalyzed ortho-/meta-C-H-annulation of biphenyl amines with 1,6-enynes. This regioselective non-rollover cyclometallation was achieved through meticulous tuning of electronic factors of both the partners. This method is applicable to a wide range of protected o-arylanilines and enynes, and results in the regioselective preparation of benzo[f]isoindolyl derivatives in high yields with good diastereoselectivity (with respect to two types of stereogenic elements). Certain essential control experiments and kinetic isotope effect (KIE) studies were undertaken to elucidate the reaction mechanism, while subsequent transformations and a scale-up reaction were performed to substantiate the sturdiness of the transformation.