Age-related macular degeneration (AMD) causes severe visual loss in the elderly; early identification of AMD risk could help slow or prevent disease progression. Toward the discovery of AMD biomarkers, we quantified plasma protein Ne-carboxymethyllysine (CML) and pentosidine from 58 AMD and 32 control donors. CML and pentosidine are advanced glycation endproducts that are abundant in Bruch’s membrane, the extracellular matrix separating the retinal pigment epithelium from the blood-bearing choriocapillaris. We measured CML and pentosidine by LC-MS/MS and LC-fluorimetry, respectively, and found higher mean levels of CML (~54%) and pentosidine (~64%) in AMD (p < 0.0001) relative to normal controls. Plasma protein fructosyl-lysine, a marker of early glycation, was found by amino acid analysis to be in equal amounts in control and non-diabetic AMD donors, supporting an association between AMD and increased levels of CML and pentosidine, independent of other diseases like diabetes. Carboxyethylpyrrole (CEP), i.e., an oxidative modification from docosahexaenoate-containing lipids and also abundant in AMD Bruch’s membrane, was elevated ~ 86% in the AMD cohort but autoantibody titers to CEP, CML and pentodsidine were not significantly increased. Compellingly higher mean levels of CML and pentosidine were present in AMD plasma protein over a broad age range. Receiver operating curves indicate that CML, CEP adducts, and pentosidine alone discriminated between AMD and control subjects with 78%, 79%, and 88% accuracy, respectively, while CML in combination with pentosidine provided ~89% accuracy and CEP plus pentosidine provided ~ 92% accuracy. Pentosidine levels appeared slightly altered in AMD patients with hypertension and cardiovascular disease, indicating further studies are warranted. Overall, this study supports the potential utility of plasma protein CML and pentosidine as biomarkers for assessing AMD risk and susceptibility, particularly in combination with CEP adducts and with concurrent analyses of fructosyl-lysine to detect confounding factors.