The prevalence of smoking among Croatian adolescents is alarmingly high, but no previous study has prospectively examined the sport- and academic-factors associated with smoking and smoking initiation. This study aimed to prospectively examine the associations between scholastic (educational) achievement and sport factors and smoking in 16- to 18-year-old adolescents. This two-year prospective cohort study included 644 adolescents who were 16 years of age at baseline (46% females). Baseline testing was implemented at the beginning of the 3rd year of high school (September 2014) when participants were 16 years old. Follow-up testing was completed at the end of the fourth year of high school, which occurred 20 months later. The evaluated predictor variables were educational-achievement- and sport-related-factors. The outcome variables were (i) smoking at baseline; (ii) smoking at follow-up; and (iii) smoking initiation over the course of the study. We assessed the associations between predictors and outcomes using logistic regression models adjusted for age, gender, socioeconomic status, and conflict with parents. The educational variables were consistently associated with smoking, with lower grade-point-average (Baseline: odd ratio (OR): 2.01, 95% confidence interval (CI): 1.61–2.55; Follow-up: 1.59, 1.31–1.94), more frequent absence from school (Baseline: OR: 1.40, 95% CI: 1.19–1.69; Follow-up: 1.30, 1.08–1.58), and lower behavioral grades (Baseline: OR: 1.80, 95% CI: 1.10–2.89; Follow-up: 1.57, 1.03–2.41) in children who smoke. Adolescents who reported quitting sports were at greater odds of being smokers (Baseline: 2.07, 1.31–3.32; Follow-up: 1.66, 1.09–2.56). Sport competitive achievement at baseline was protective against smoking initiation during following two-year period (0.45, 0.21–0.91). While the influence of the educational variables on smoking initiation has been found to be established earlier; sport achievement was identified as a significant protective factor against initiating smoking in older adolescents. Results should be used in development of an anti-smoking preventive campaign in older adolescents.