Fourier-transform infrared (FTIR) spectroscopy is extensively employed to analyze chemical composition of asphalt binders. There is an urgent need to establish a chemo-mechanical link between the chemical data from FTIR spectra and the rheological characteristics of asphalt binders. In this study, based on the FTIR analysis of 40 asphalt binders derived from two different base binders, at various rejuvenator dosages and aging states, the resulting spectra were assessed using the multivariate analysis method principal component analysis (PCA). Rheological properties of the asphalt binder, obtained from frequency sweep tests, the 2S2P1D micro-mechanical model, and poker-chip tests, were also incorporated into the PCA analysis. Correlations between each pair of properties can be revealed from the loading plot generated by the PCA. Additionally, the asphalt-binder samples were effectively distinguished based on their aging states and degrees of rejuvenation. Thereby, highly aged binders tended to have higher viscosity, strength, complex modulus, α (a constant in 2S2P1D model), and τ (characteristic time), and their FTIR absorption of the carbonyl group, sulfur-containing functional groups, and aromatic C-H bending vibration were more pronounced. Highly rejuvenated binders contained larger ductility, phase angle, k , and h (exponents of two parabolic creep elements) with more significant FTIR absorption of asymmetric and symmetric C-H stretching vibrations of CH2 and CH3 group, and aliphatic -CH2. Binders based on different bases showed good agreement in chemo-mechanical correlations. The results of this study validated PCA as an effective tool to understand chemo-mechanical interactions in asphalt binder and mechanisms of rejuvenation and aging.