In this study, structural, mechanical, and chemical changes of one-sided thermally loaded carbon fiber reinforced polymers (CFRPs) are investigated. The aim is to test and reliably predict residual strength and delamination depth by using infrared spectroscopy. CFRP of different thicknesses (HexPly ® 8552/ IM7) were irradiated at varying heat fluxes over various time intervals. The inhomogeneously distributed matrix degradation was analyzed by means of attenuated total reflection Fourier transform infrared spectroscopy with a depth resolution of 0.2 mm. Residual interlaminar shear strength (ILSS) was determined and microfocused computed X-ray tomography was used to measure the delamination depth. Principal component analyses were performed to show which information in the infrared spectra is affected by thermal loading. Furthermore, the combination of spectra taken at different depths of the CFRP can be used to develop partial least squares regression models to predict ILSS and delamination depth. Despite an inhomogenous distribution of thermal damage, precise predictions of ILSS and delamination depth with models considering varying sample thicknesses and heat fluxes were achieved.