Purpose: The current study addresses a gap in the literature regarding syntactic development of adolescent boys with fragile X syndrome (FXS) and Down syndrome (DS). Specifically, we ask whether syntactic skills plateau or continue to change during adolescence for these groups and whether the profile of syntactic change differs between boys with FXS and those with DS. Method: Participants were 38 boys with FXS (with and without autism) and 20 boys with DS between the ages of 10 and 16 years, as well as 33 boys who were neurotypical between the ages of 3 and 8 years at study entry. Trained examiners evaluated the participants annually for four consecutive years. The evaluation included standardized language assessments and a conversational language sample, which was analyzed using mean length of utterance-morphemes and the Index of Productive Syntax. For each measure, we fit a series of candidate models, including the intercept-only model and models with nonverbal cognition and maternal IQ as moderators. We then used Akaike's information criteria-corrected to determine which model in a candidate set had the most empirical evidence. Results: Our between-groups results indicated that FXS and DS have distinct syntactic profiles. However, our growth analyses and moderator analyses yielded mixed results. For most measures, the most likely models suggest that there is no plateau in the growth of syntactic skills for boys with FXS or DS and that nonverbal cognition is associated with the rate of change. Conclusions: These results suggest that syntactic change continues to occur throughout adolescence for boys with FXS or DS. The results also indicate that the growth profiles are distinct between the two groups. Future research with more participants from more diverse backgrounds would add more clarity to these findings.