Non-suicidal self-injury (NSSI) is among the most frequent maladaptive behaviors reported in adolescence, with prevalence rates around 18–22% in community samples worldwide. The onset of NSSI typically occurs between early and middle adolescence, with a peak during middle adolescence (14–15 years) and a subsequent decline during late adolescence. This study investigated the growth curves of NSSI across four years during adolescence, analyzing simultaneously the probability of engagement in NSSI at least once (i.e., prevalence) and the frequency of engagement once initiated (i.e., severity). Furthermore, the study examined the predicting role of effortful control on NSSI over time (time-varying effects), net of other key risk factors for NSSI, such as anxiety-depression and bullying victimization. A sample of 430 Italian adolescents enrolled in Grade 9 at baseline was involved in the study. Based on the Latent Growth Curve Zero-inflated Poisson methodology, the results indicated a negative quadratic trend of both NSSI prevalence, with an increase between T1 and T3 followed by a decrease in the subsequent wave, and NSSI frequency once initiated, with a peak at T2 followed by a decline over time. The results also showed that adolescents who reported low effortful control abilities had a heightened probability of involvement in NSSI at each time point, whereas no significant association was found with NSSI frequency once initiated. Findings from this study offer important insights into the developmental course of NSSI and point out the need for future in-depth investigations of the mechanisms that might underlie NSSI prevalence and severity throughout adolescence.