Objectives <p>To explore patterns of combinations of mental disorders and their association with mortality using data from the UK Biobank, a large middle-aged and elderly cohort.</p> Methods <p>This longitudinal cohort study analyzed data from approximately 160,000 UK Biobank participants who completed a Mental Health Questionnaire. We identified six probable lifetime mental disorders, examined their combinations using association rule mining, and estimated age and sex-adjusted mortality rate ratios (MRRs) for each disorder and combination.</p> Results <p>Combinations of mental disorders were found in approximately 30% of questionnaire completers identified with at least one probable lifetime mental disorder. Most combinations involved depression and/or anxiety. Combinations of mental disorders were generally associated with higher mortality, especially those including alcohol and substance use disorders. The highest MRR was observed for alcohol use disorder plus substance use disorder plus psychotic experience (MRR = 4.94, 95% CI [2.57–9.5]).</p> Conclusions <p>In a large middle-aged and elderly cohort in the UK, combinations of probable lifetime mental disorders identified via an online questionnaire were common and generally associated with higher mortality.</p> Clinical trial number <p>Not applicable.</p>