Cyclic peptides are important synthetic targets due to their constrained conformation, enhanced metabolic stability and improved bioavailability, which combine to make them promising lead compounds for drug candidates. They are typically synthesized by a multi-step sequence of carefully orchestrated protecting group manipulations and cyclization of side-chain protected linear precursors. In the present manuscript we disclose an alternative approach to the synthesis of peptide macrocycles by the α-ketoacid–hydroxylamine (KAHA) ligation. This reaction allows readily prepared linear peptides to be cyclized without reagents or side-chain protecting groups and delivers a native backbone amide bond at the ligation site. The precursors are prepared with Fmoc-based solid phase peptide synthesis using reagents that we have previously disclosed. No post-cyclization manipulations or deprotections other than purification are required. This protocol was applied to five different cyclic peptide natural products of varying ring sizes and side chain functionalities.