Cochineal dyes constitute paradigmatic organic compounds that guide in the elucidation of historic cultural and economical exchanges. This study combines liquid chromatography and high-resolution tandem mass spectrometry to assess the degradation products of the organic dyes of American cochineal collected from the cargo of a 16th century sunken wreck. The identification of biological materials of historical and archeological origin is often challenging due to molecular degradation. In this scenario, the mapping of the chemical routes underlying the fate of the organic and biochemical compounds employed as taxonomic biomarkers becomes of crucial importance. This work shows that, under harsh environmental conditions, the original carminic and (flavo) kermesic acid structures of cochineal dyes are prone to chemical transformation, typically losing the carboxylic acid and glucoside groups. The anthraquinone core is preserved in the majority of degradation products identified in this study, with eventual side chains reminiscent of a partial degradation of the glucoside moiety. The comparison of these observations with the analysis of modern cochineal samples allows us to lay out an updated chart of dye compounds and degradation products which should constitute a seminal benchmark for future biomolecular analysis of historic and archeological dye materials.