Individuals with intellectual and developmental disabilities (IDD) are at a high risk of experiencing pain. Pain management requires assessment, a challenging mission considering the impaired communication skills in IDD. We analyzed subjective and objective responses following calibrated experimental stimuli to determine whether they can differentiate between painful and non-painful states, and adequately quantify pain among individuals with IDD. Eighteen adults with IDD and 21 healthy controls (HC) received experimental pressure stimuli (innocuous, mildly noxious, and moderately noxious). Facial expressions (analyzed with the Facial Action Coding System (FACS)) and autonomic function (heart rate, heart rate variability (HRV), pulse, and galvanic skin response (GSR)) were continuously monitored, and self-reports using a pyramid and a numeric scale were obtained. Significant stimulus-response relationships were observed for the FACS and pyramid scores (but not for the numeric scores), and specific action units could differentiate between the noxious levels among the IDD group. FACS scores of the IDD group were higher and steeper than those of HC. HRV was overall lower among the IDD group, and GSR increased during noxious stimulation in both groups. In conclusion, the facial expressions and self-reports seem to reliably detect and quantify pain among individuals with mild-moderate IDD; their enhanced responses may indicate increased pain sensitivity that requires careful clinical consideration.