Introduction: Individuals with Down syndrome (DS) and IDD have lower psychiatric disorders rates than other individuals with IDD, and more information is needed about possible unique mental health needs of this group. Method: De-identified intake data for individuals with IDD, 101 with DS (mean age 27) and 4,366 without DS (mean age 25) served in START, a tertiary care mental health crisis response program, were reviewed. Behavioral health, and medical factors were investigated using Chi-squared or t-tests at p < 0.05, and logistic/linear regression models. Results: People with DS referred for behavioral health conditions were less likely than counterparts with IDD without DS, to be diagnosed with ADHD (OR = 0.47), ASD (OR = 0.31), and to be taking psychotropics (OR = 0.23), and to have significantly lower irritability/agitation, hyperactivity/noncompliance, and inappropriate speech ABC subscale scores while having more endocrine conditions (OR = 2.61). Discussion: In this study, individuals with IDD with and without DS referred for mental health challenges showed varied physical and mental health conditions.