Risk sexual behaviours are known as a threat to health and wellbeing of adolescents. Although there are standard sexual education curriculums in Thai schools, most schools use traditional teaching methods rather than participatory teaching activities. This study aimed to (i) develop ‘Teen-Strong’ programme by combining the concept of the World Health Organization’s life skills programme with Thai sexual education curriculum and (ii) investigate the association of Teen-Strong programme with knowledge and decision-making regarding risky sexual behaviours and teenage pregnancy in Thai adolescents. The Teen-Strong programme was developed by means of experts review and cognitive interviewing process and evaluated in 66 adolescents in Grades 7–9 from six schools in southern Thailand. Twenty-six students were assigned to the experimental group (attended Teen-Strong programme and standard sexual education) and 40 to the control group (attended only the standard sexual education). A pre–post-test quasi-experimental design was used and the Teen-Strong questionnaire (TSQ) was administered to measure knowledge and decision-making at three time points: before (T1), immediately after (T2) and 1 month after (T3) attending the programme. A 2 × 3 mixed-design ANOVA was used to analyse the data. TSQ scores in the experimental and control groups were higher at T2 and T3 as compared with T1. Mean increase in TSQ scores at T2 and T3 compared with T1 were significantly higher in the experiment than the control group [T2 vs. T1: t (64) = 4.07, p-values < 0.0001; T3 vs. T1: t (64) = 3.32, p-values = 0.017]. This study showed that Teen-Strong programme could increase adolescent’s knowledge and decision-making skills regarding risk sexual behaviours.