Background: Psychopathology is highly prevalent in adolescents and adults with several genetic syndromes associated with intellectual disability, including Williams syndrome (WS), fragile X syndrome (FXS) and Prader–Willi syndrome (PWS). However, little is known about associated risk factors. This study aims to identify whether age, health difficulties, adaptive ability and sensory processing impairments may predict or influence psychopathology in these groups. Methods: A questionnaire study was conducted with 111 parents/carers of individuals over the age of 12 (WS = 35, FXS = 50, PWS = 26; 74 were male). The mean age of the sample was 26.41, SD = 10.38. Results: Multiple regression analyses were utilised to examine predictors of psychopathology at group level. For the WS group, increased current health difficulties and sensory processing impairments predicted increased psychiatric disturbance F5,28 = 8.16, P < .0001, adj R2 = .52. In PWS, only poorer adaptive ability was influential in predicting increased overall psychiatric disturbance (B‐1.41, P = .001), generalised anxiety (B = −0.37, P = .006) and hyperactivity (B = −0.38, P = .003). There were no significant predictors of psychopathology for individuals with FXS. Conclusion: This study highlights dissociations in the risk factors of psychopathology between the three syndromes. Adaptive ability may contribute to the development and maintenance of psychopathology in PWS, whereas health difficulties and sensory processing may be influential for individuals with WS. Identification of risk factors may be beneficial in assisting diagnosis and informing prevention strategies for psychiatric difficulties.