The human face is a powerful elicitor of emotion, which induces autonomic nervous system responses. In this study, we explored physiological arousal and reactivity to affective facial displays shown in person and through video-mediated communication. We compared measures of physiological arousal and reactivity in typically developing individuals and those with the developmental disorders Williams syndrome (WS) and autism spectrum disorder (ASD). Participants attended to facial displays of happy, sad, and neutral expressions via live and video-mediated communication. Skin conductance level (SCL) indicated that live faces, but not video-mediated faces, increased arousal, especially for typically developing individuals and those with WS. There was less increase of SCL, and physiological reactivity was comparable for live and video-mediated faces in ASD. In typical development and WS, physiological reactivity was greater for live than for video-mediated communication. Individuals with WS showed lower SCL than typically developing individuals, suggesting possible hypoarousal in this group, even though they showed an increase in arousal for faces. The results are discussed in terms of the use of video-mediated communication with typically and atypically developing individuals and atypicalities of physiological arousal across neurodevelopmental disorder groups.