Cross-sectional studies indicate that mental disorders are inversely associated with quality of life (QoL) and that the magnitude of the negative correlation varies across disorders. The aims of this study were to examine whether QoL decreases after new onset of psychiatric disorders and to characterize variations across disorders. Data were drawn from a longitudinal study representative of the adult US population. Changes were examined in QoL, as measured by the Short Form–12 version 2, after incidence of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), disorders at wave 2 in individuals without the given disorder at wave 1. A subanalysis examined change of QoL after incidence of mental disorders in individuals without a history of any mental disorder. With the exception of alcohol abuse, new incidence of each examined DSM-IV disorder was associated with a decrement in QoL, being the largest for major depressive disorder and generalized anxiety disorder. Incidence of these disorders was associated with a decrease in QoL even in individuals without history or presence of any other mental disorder. Although the incidence of most DSM-IV disorders is associated with a decrement in QoL, mood and anxiety disorders have the largest impact.