Abstract Background Accumulation of advanced glycation end-products (AGEs) in skeletal muscle has been implicated in development of sarcopenia. Aim To obtain further insight in the pathophysiology of sarcopenia, we studied its relationship with skin AGEs in the general population. Methods In a cross-sectional analysis, 2744 participants of northern European background, mean age 74.1 years, were included from the Rotterdam Study. Skin AGEs were measured as skin autofluorescence (SAF) using AGE ReaderTM, appendicular skeletal mass index (ASMI) using insight dual-energy X-ray absorptiometry, hand grip strength (HGS) using a hydraulic hand dynamometer, and, in a subgroup, gait speed (GS) measured on an electronic walkway (n = 2080). We defined probable sarcopenia (low HGS) and confirmed sarcopenia (low HGS and low ASMI) based on the European Working Group on Sarcopenia in Older People (EWGSOP2) revised criteria cutoffs. Multivariate linear and logistic regression were performed adjusting for age, sex, body fat percentage, height, renal function, diabetes, and smoking status. Results The prevalence of low ASMI was 7.7%; probable sarcopenia, 24%, slow GS, 3%; and confirmed sarcopenia, 3.5%. SAF was inversely associated with ASMI [β −0.062 (95% CI −0.092, −0.032)], HGS [β −0.051 (95% CI −0.075, −0.026)], and GS [β −0.074 (95% CI −0.116, −0.033)]. A 1-unit increase in SAF was associated with higher odds of probable sarcopenia [odds ratio (OR) 1.36 (95% CI 1.09, 1.68)] and confirmed sarcopenia [OR 2.01 (95% CI 1.33, 3.06)]. Conclusion Higher skin AGEs are associated with higher sarcopenia prevalence. We call for future longitudinal studies to explore the role of SAF as a potential biomarker of sarcopenia.