We examined potential phenotypic differences in eye gaze avoidance exhibited by boys with autism spectrum disorder (ASD) and boys with fragile X syndrome (FXS). In Study 1, the Eye Contact Avoidance Scale (ECAS) was administered to caregivers of boys aged 7–18 years with FXS (n = 148), ASD (n = 168), and mixed developmental disabilities (MDD; n = 128). In Study 2, subsets of boys with FXS (n = 31) and boys with ASD (n = 25) received a brief behavioral treatment probe to improve eye contact. Results showed that boys with FXS obtained significantly higher scores on the ECAS compared to boys with ASD and MDD. Exposure to the brief behavioral treatment probe resulted in significant decreases in scores for boys with FXS, but not for boys with ASD.