Objective: Advanced glycation end-products (AGEs) may contribute to the pathogenesis of atherosclerotic cardiovascular disease (ASCVD), potentially influencing its development and progression differently at various life stages. This study aimed to elucidate the associations between AGEs and the risk of ASCVD across different age groups. Methods: In this cross-sectional study, 1,240 subjects were enrolled and divided into three groups (Group I, 20-39 years old, n = 468; Group II, 40-59 years old, n = 471; Group III, 60-79 years old, n = 301). Skin AGEs were measured by skin autofluorescence (SAF). ASCVD risk was assessed by a validated Framingham risk score calculator. Other proven ASCVD risk factors were also measured, including glycosylated hemoglobin, uric acid, lipid profile, homocysteine, and cystatin C. Results: An increasing trend in skin AGEs was observed from Group I to Group III. Skin AGEs were significantly associated with ASCVD risk in all subjects (OR 1.029, 95% CI 1.003-1.056, P = 0.018), independent of some of the proven cardiovascular risk factors. This association was particularly significant in individuals aged 40-59 and 60-79 (OR = 1.047, 95% CI: 1.025-1.069; OR = 1.022, 95% CI: 1.002-1.042; both P < 0.05). ROC analysis showed that skin AGEs predicted the diagnosis of medium or high ASCVD risk in the pooled group, Group II, and Group III. Conclusion: Our study substantiates that skin AGEs play an important role as an independent risk factor for ASCVD, highlighting their significance beyond traditional risk assessment models, particularly in middle-aged and older populations.