The are sex differences in cardiometabolic risk factors in type 2 diabetes mellitus (T2DM) as well as the age at disease onset. However, the impact of these risk factors on the age at onset of T2DM is less known in the Ghanaian population. An understanding of the differential impact of cardiometabolic risk factors on the age at onset on T2DM may lead to sex-specific interventions in preventive and management strategies for T2DM. The study was cross-sectional from January to June 2019 at the Bolgatanga regional hospital. The study involved 163 T2DM patients (Female = 103, Male = 60), aged from 25 to 70 years. The body mass index (BMI) and the waist-to-hip ratio (WHR) were measured following standardized anthropometric techniques. Fasting venous blood samples were collected and analyzed for cardiometabolic risk factors including total cholesterol (TCHOL) and low-density lipoprotein (LDL) cholesterol. While TCHOL was higher in males than females (mean [SD]: F = .78 [1.37], M = 4.27 [1.39]) and LDL higher in females than males (mean [SD]: [F = 4.33 [1.22], M = 3.87 [1.26]), these did not, however, attain conventional statistical significance for TCHOL (t = 1.985, p = 0.05) and LDL (t = 2.001, p = 0.05). There were however, significant interactions between sex and the age at disease onset on TCHOL (t = -2.816, p = 0.006) and LDL (t = -2.874, p = 0.005), which were independent of the BMI, WHR and disease duration. The relationship between the age at disease onset and that of TCHOL and LDL were positive in females but negative in males. Fasting plasma TCHOL and LDL increases with increasing age at onset of T2DM in females but decreases in males. Strategies for the prevention and management of T2DM should be sex-specific. Females with T2DM should be given more attention regarding their fasting plasma cholesterol (total) and LDL cholesterol as they are more likely than men to have increased levels of these lipids with increasing age at disease onset.