Research has found an association between irritability and suicidal thoughts and behaviors (STB) in children and adolescents, but the overall evidence has been mixed and the nature of this association remains unclear. In this study, we investigated whether the link between irritability and STB might be more pronounced among older youth and those with lower levels of hope. Participants were 142 children and adolescents (ages 6–18) referred for mental health services at a university outpatient clinic. At intake, clinicians administered self-report measures assessing irritability, STB, hope, and depression. Multiple regression models with robust maximum likelihood estimation were used to test irritability’s association with STB, as well as age and hope as moderators. Irritability, hope, and age all showed significant associations with STB. Further, hope and age moderated the associations between irritability and STB; specifically, the link between irritability and STB was evident only at older ages (among adolescents, not children) and only at lower levels of hope. These findings are consistent with the view that hope may be a protective factor, and adolescence a vulnerability factor, in the association between irritability and STB. Results may help explain previous mixed findings on this association while also underscoring the role of irritability as a risk factor. Further research is warranted to better understand irritability and hope as transdiagnostic mechanisms in STB from childhood through adulthood, and through other informants and methods.