A decline in the inherent quality of bone tissue is a contributor to the age-related increase in fracture risk. Although this is well known, the important biochemical factors of bone quality have yet to be identified using Raman spectroscopy (RS), a non-destructive, inelastic light scattering technique. To identify potential RS predictors of fracture risk, we applied principal component analysis (PCA) to 558 Raman spectra (370 cm−1 – 1720 cm−1) of human cortical bone acquired from 62 female and male donors (9 spectra each) spanning adulthood (21 – 101 yo). Spectra were analyzed prior to R-curve, non-linear fracture mechanics that delineates crack initiation (Kinit) from crack growth toughness (Kgrow). The traditional ν1Phosphate peak per Amide I peak (mineral-to-matrix ratio) weakly correlated with Kinit (r = 0.341, p =0.0067) and overall crack growth toughness (J-int: r = 0.331, p =0.0086). Sub-peak ratios of the Amide I band that are related to the secondary structure of type 1 collagen did not correlate with the fracture toughness properties. In the full spectrum analysis, one principal component (PC5) correlated with all of the mechanical properties (Kinit: r = −0.467, Kgrow: r = −0.375, and J-int: r = −0.428; p < 0.0067). More importantly, when known predictors of fracture toughness, namely age and/or volumetric bone mineral density (vBMD), were included in general linear models as covariates, several principal components helped explain 45.0% (PC5) to 48.5% (PC7), 31.4% (PC6), and 25.8% (PC7) of the variance in Kinit, Kgrow, and J-int, respectively. Deriving spectral features from full spectrum analysis may improve the ability of RS, a clinically viable technology, to assess fracture risk.