Purpose: This study investigated intonation prosody in Persian children with Down syndrome (DS) and typically developing (TD) children. To this end, this study examined several intonation features, including pitch accents, boundary tones, and nuclear pitch accents, across different sentence types to understand the intonation prosody in Persian-speaking individuals with DS and to identify similarities and differences between children with DS and their TD peers. Method: Five children with DS (two boys and three girls under 11 years of age) and 22 age-matched TD children (11 boys and 11 girls) participated in this study, producing informal Persian utterances that were recorded using a Shure microphone and analyzed using the PRAAT software. Conclusions: This study found that children with DS showed differences in the intonation prosody, including errors in articulating non-monosyllabic words and variations in pitch tracks. Furthermore, children with DS showed variations in boundary tones and nuclear pitch accents (NPAs), particularly in level boundary tones (Abolhasanizadeh et al., Lingua 122(13):1380–1394, 2012), compared to their TD peers. These findings could help speech-language therapists develop more effective intervention strategies for children with DS, particularly in the area of the intonation prosody. Overall, this study contributes to a better understanding of the communication needs of children with DS and suggests potential strategies to enhance their developmental support through effective interventions.