Background Identifying the clustering patterns of health risk behaviors (HRBs) within individuals and their health impacts are essential to develop lifestyle promotion strategies. This study aimed to explore the clustering of a range of HRBs and the associations between such identified clusters and diabetes in Southern Chinese adults. Methods Data from 5,734 adults aged 35–75 years and underwent health examinations from November 2012 to December 2013 at a tertiary hospital in Guangzhou were analyzed. Behavioral characteristics, including smoking, alcohol use, physical activity, and sleep duration and quality, were measured by questionnaires. Latent class analysis was conducted by gender to identify HRBs clustering patterns, and logistic regression models were used to estimate the associations between behavioral patterns and diabetes. Results Three distinct behavioral clusters emerged in both genders. Male classes were defined as: (1) healthy lifestyle (Class 1, 62.9%); (2) cumulate harmful habits (Class 2, 27.1%); (3) poor sleep and risky habits (Class 3, 10.0%). Female classes were: (1) healthy lifestyle (Class 1, 83.0%); (2) inactive, daytime dysfunction (Class 2, 5.7%); (3) poor sleep habits (Class 3, 11.3%). Individuals of Class 2 and Class 3 showed a higher likelihood of diabetes across genders (multivariable-adjusted ORs [95% CIs], 2.03 [1.49–2.76] and 2.61 [1.78–3.81] among males, 2.64 [1.16–5.98] and 1.81 [1.07–3.06] among females) when compared with those of Class 1. Conclusions Our data provided additional evidence of HRBs clustering among adults, and such clustering was associated with an increased risk of diabetes. These findings have implications for identifying vulnerable subgroups and developing diabetes prevention programs.