Pyroglutamate is a cyclic N-terminal post-translational modification that occurs in both proteins and peptide hormones. The prevalence and biological roles of pyroglutamate are little understood, in part due to limited tools to identify, quantify, and manipulate its pyrrolidinone structure. Selective modification of pyroglutamate residues in complex polypeptides may provide unique tools to better understand its biological roles and to allow late-stage diversification of biologically active pyroglutamate-containing sequences. This work describes a copper-catalyzed N-H cross-coupling of unprotected peptides that is selective for N-terminal pyroglutamate residues. The reaction is operationally simple under mild conditions and tolerates all canonical residues. Mechanistic studies point to a key role for a multidentate copper-binding mode of the extended polypeptide structure in delivering the observed reactivity. The reaction allows for direct labeling and identification of a pyroglutamate hormone present in porcine intestinal extracts.