For individuals with intellectual and developmental disabilities (IDD), the understanding and expression of empathy and its various components can be challenging. However, different etiologies can elucidate various strengths and weaknesses related to empathy. The present study examined the specific relationship of empathy and social skills for individuals with autism (AD), Williams syndrome (WS), Down syndrome (DS), and a non-disabled (ND) control group. The research questions for the current study were (a) Do caregiver ratings of empathy and social skills differ across individuals with AD, WS, DS, and ND?; and (b) Are there differences in the relationship between empathy skills and social skills within and across groups? The total sample (N = 120) included caregivers of 30 individuals diagnosed with AD (mean age = 10.73 years), 30 individuals diagnosed with WS (mean age = 12.07 years), 30 individuals with DS (mean age = 11.53 years), and 30 ND individuals (mean age = 10.90 years). Caregivers were asked to complete the children's version of the Empathy Quotient and the Social Responsiveness Scale (2nd Edition). According to caregiver reports, AD individuals present with lower empathy skills compared to WS, DS, and ND individuals. Differences between groups were also demonstrated regarding the relationship between empathy and social skills. More specifically, for WS individuals, lower empathy skills were not significantly correlated with social motivation. The results highlight that differences in empathy and social skills should be accounted for in empathy-related interventions and underscores the importance of developing etiology-specific interventions.