Background: Lifetime trends in total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) with age remain unclear. Methods: A cross-sectional study with data from 103,461 and 74,706 men and women, respectively, was conducted to explore lifetime trends in the above-mentioned lipid parameters with age; turning points of age were established using age stratification and were validated by fitted multivariate linear logic regression modeling. Findings: Age was an independent factor extensively associated with lipid levels in both sexes, when adjusted for serum glucose, BMI, lifestyle, drinking and smoking. Age was positively associated with TC, logarithm transformed TG (LnTG) and LDL-C levels in men ≤ 40, ≤ 40 and ≤ 60 years old (yo); and in women ≤ 60, ≤ 70 and ≤ 60 yo, respectively. Conversely, age was negatively associated with TC, LnTG and LDL-C levels in men ≥ 61 ≥ 41 and ≥ 61 yo; and in women ≥ 61 and ≥ 71 and ≥ 61 yo, respectively. TC, TG and LDL-C levels of women were initially lower than those in men and then surpassed those of men in the age groups of 51-55, 61-65 and 51- 55 yo. The trends in HDL-C levels with age are relatively irregular, while women's HDL-C levels are higher than men's throughout all age groups. . Interpretation: Age-related trends in lipid levels and sex differences should be fully considered in the definition of dyslipidemia, atherosclerotic cardiovascular disease (ASCVD) risk assessment, and the initiation/goals of statin therapy. Funding Statement: This research was supported by the Regional Fund Project of the National Natural Science Foundation of China (Serial number: 81460326), Joint Special Funds from the Yunnan Province Science and Technology Department and Department of Applied Basic Research of Kunming Medical University (Serial number: 2018FE001-081), and the Special Funds for Training High-level Health Technical Talents in Yunnan Province (Serial number: D-201644). Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: This study was conducted in accordance with the principles of the World Medical Association’s Declaration of Helsinki. The study protocol was approved by the Review Board of our hospital. Written informed consent was obtained from all participants to join this study and for the publication of their data.