This study aimed to examine differences in CVD risk factors across four crosstabulated groups according to health-related physical fitness index (PFI, composite index of standing long jump, 50-m test, and 800-or 1000-m run/walk) and waist circumference (WC) in Guangzhou youth. Participants comprised 588 males and 579 females aged 11-18years from Guangzhou, China. They were cross-tabulated into four groups according to WC and PFI, namely, Low-WC/High-PFI, High-WC/Low-PFI, Low-WC/Low-PFI, and High-WC/High-PFI. A CVD risk score was derived from six established CVD risk factors, i.e., blood pressure (BP), triglycerides (TG), fasting total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and TC: HDL-C. For both genders, lower BP values were observed in the Low-WC group compared with the High-WC group with the same fitness level (p<0.05). In boys, participants in the Low-WC/Low-PFI group also had lower BP than those in the High-WC/High-PFI group (p<0.05). Lower TC, LDL-C, TC: HDL-C, and higher HDL-C were also found in the Low-WC groups than in the High-WC groups in boys (p<0.05). A general trend of lower blood lipids and glucose for both boys and girls in the High-PFI group compared with the Low-PFI group was also observed. Higher CVD risk scores were only observed in the High-WC group compared with the Low-WC group with the same PFI level for boys (p<0.05). We can concluded that clustering of CVD risk factors was inversely related to WC, and physical fitness may play a positive effect on reducing the hazards of abdominal obesity.