Background Cigarette smoking and physical inactivity are two critical risk factors for noncommunicable diseases and all-cause mortality. However, few studies have compared the long-term trajectories of both behaviors, as well as multilevel factors associated with trajectory patterns. Using the National Longitudinal Study of Adolescent to Adult Health (Add Health) Wave I through V survey data, this study characterized distinct subgroups of the population sharing similar patterns of physical activity (PA) and cigarette smoking from adolescence to adulthood, as well as predictors of subgroup membership. Methods Using the Add Health Wave I through V survey data, we identified the optimal number of latent classes and class-specific trajectories of PA and cigarette smoking from early adolescence to adulthood, fitting latent growth mixture models with standardized PA score and past 30-day cigarette smoking intensity as outcome measures and age as a continuous time variable. Associations of baseline sociodemographic factors, neighborhood characteristics, and sociopsychological factors with trajectory class membership were assessed using multinomial logistic regression. Results We identified three distinct subgroups of PA trajectories in the study population: moderately active group (N=1067, 5%), persistently inactive group (N=14257, 69%) and worsening activity group (N=5410, 26%). Similarly for cigarette smoking, we identified three distinct trajectory subgroups: persistent non-smoker (N=14939, 72%), gradual quitter (N=2357, 11%), and progressing smoker (N=3393, 16%). Sex, race/ethnicity, neighborhood environment and perceived peer support during adolescence were significant predictors of physical activity and cigarette smoking trajectory subgroup membership from early adolescence to adulthood. Conclusion There are three distinct subgroups of individuals sharing similar both PA and cigarette smoking behavioral profile from adolescence to adulthood in the Add Health study population. Modifiable risk factors such as neighborhood environment and relationship to peers during adolescence can be key to designing effective behavioral interventions for long-term PA promotion and cigarette smoking cessation.