Background <p>Educational attainment (EA) was associated with lifestyle behaviors and underlying mental disorders. However, the causality remained poorly understood. This study aimed to elucidate the causal association between EA and mental disorders while exploring the mediation role of lifestyle factors.</p> Methods <p>A two-step Mendelian randomization (MR) analysis was performed to evaluate the mediation role of lifestyle factors in the relationship between EA and mental disorders. The total effects of years of education (EduYears) and college completion (College) on 31 lifestyle factors and 7 mental disorders were estimated using univariable MR. Multivariable MR was utilized to assess the independent effects of lifestyle factors on mental disorders. Mediation effects were calculated for factors significantly associated with both EA and mental disorders.</p> Results <p>EduYears was significantly associated with anorexia nervosa (AN), major depression disorder (MDD), post-traumatic stress disorder (PTSD), and attention deficit hyperactivity disorder (ADHD), with <i>OR</i> (95% <i>CIs</i>) of 0.96 (0.92, 0.99), 0.97 (0.94, 1.00), 0.94 (0.91, 0.97), and 0.84 (0.82, 0.87), respectively. Similarly, genetically determined College was inversely associated with AN, MDD, PTSD, and ADHD. Smoking initiation, processed meat intake, beef intake, and cereal intake mediated the effect of EA on mental disorders from 9% to 31%.</p> Conclusion <p>This study indicated the causal effect of EA on AN, MDD, PTSD, and ADHD. The mediation analysis indicated that smoking and diet partially explained the effect. The results underscored the significance of EA and lifestyle factors in mental health policies.</p>