Background There is a need for brief screening methods for psychiatric disorders in clinical practice. This study assesses the validity and accuracy of a brief self-report screening questionnaire, the Web Screening Questionnaire (WSQ), in detecting psychiatric disorders in a study group comprising the general population and psychiatric outpatients aged 18 years and older. Objective The aim of this study was to investigate whether the WSQ is an adequate test to screen for the presence of depressive and anxiety disorders in clinical practice. Methods Participants were 1292 adults (1117 subjects from the general population and 175 psychiatric outpatients), aged 18 to 65 years. The discriminant characteristics of the WSQ were examined in relation to the (“gold standard”) Mini-International Neuropsychiatric Interview-Plus (MINI-Plus) disorders, by means of sensitivity, specificity, area under the curve (AUC), and positive and negative predictive values (PPVs, NPVs). Results The specificity of the WSQ to individually detect depressive disorders, anxiety disorders, and alcohol abuse or dependence ranged from 0.89 to 0.97 for most disorders, with the exception of post-traumatic stress disorder (0.52) and specific phobia (0.73). The sensitivity values ranged from 0.67 to 1.00, with the exception of depressive disorder (0.56) and alcohol abuse or dependence (0.56). Given the low prevalence of separate disorders in the general population sample, NPVs were extremely high across disorders (≥0.97), whereas PPVs were of poor strength (range 0.02-0.33). Conclusions In this study group, the WSQ was a relatively good screening tool to identify individuals without a depressive or anxiety disorder, as it accurately identified those unlikely to suffer from these disorders (except for post-traumatic stress disorders and specific phobias). However, in case of a positive WSQ screening result, further diagnostic procedures are required.