The non-mammalian therapsids dominated the terrestrial ecosystems during the Late Paleozoic—Early Mesozoic. The cynodonts have been studied from a taxonomic, osteologic and morphological perspective. However, taphonomy using chemometrics has been barely explored. This report includes a rib and an appendicular bone of cynodonts from the Puesto Viejo Group (Mendoza, Argentina). These fossils are studied for the first time using SEM-EDX. Semi-quantitative data derived from SEM-EDX spectra is evaluated by principal component analysis to gain new insights regarding the different diagenetic pathways of bone microstructure. The multivariate model supports the distinction of different sampled areas (bone, transition zone and rock matrix), in terms of chemical parameters. Differentiation is based mainly on varying contents of Ca, P, F, Si, Al, K, O, Mn and Fe. Variable concentrations of Fe and Mn could be related to different facies (floodplain and crevasse splay). These results along with thin section petrographical analysis confirm —in one of the cases— the substitution of hydroxyapatite by fluorapatite in the bone microstructure. Fossil-diagenetic processes observed herein include substitution, fracturing, brittle deformation and different permineralization events. Permineralization stages during burial history include infilling of vascular canals, trabeculae and fractures with hematite, manganite and calcite. The presence of calcite and iron enrichment indicates local reducing conditions below water-table during precipitation. This chemometric approach to the study of Triassic cynodont remains proved useful for assessing the chemical changes in bone microstructure.