The palladium(II)-catalyzed β- and γ-alkynylation of amide C(sp<sup>3sup>)−H bonds is enabled by pyridine-based ligands. This alkynylation reaction is compatible with substrates containing α-tertiary or α-quaternary carbon centers. The β-methylene C(sp<sup>3sup>)−H bonds of various carbocyclic rings were also successfully alkynylated.