<p>The associations between distinct cognitive function trajectories and mortality risk, as well as the potential mediating pathway underlying this relationship, have not been fully elucidated. This cohort study explored the association between cognitive function trajectories and all-cause mortality and the mediating role of oral health-related quality of life (OHRQoL). A nationwide cohort of 5486 individuals aged ≥45&#xa0;years was included in this study. Longitudinal courses of cognitive function measured using the Mini-Mental State Examination (MMSE) were classified using growth mixture modeling. The OHRQoL was measured using the Geriatric Oral Health Assessment Index. The association between cognitive function trajectories and all-cause mortality was determined using a Cox model. Mediation analyses were conducted to evaluate the mediating role of OHRQoL in this association. Hazard ratios (HRs) and 95% confidence intervals (CIs) were computed. Four trajectories of cognitive function were identified: high-stable (<i>n</i> = 4469; 81.5%), moderate-increasing (<i>n</i> = 418; 7.6%), decreasing (<i>n</i> = 454; 8.3%), and low-stable (<i>n</i> = 145; 2.6%). Compared to those experiencing high-stable trajectory, individuals experiencing decreasing (HR = 1.39, 95% CI = 1.08–1.78) and low-stable (HR = 1.84, 95% CI = 1.31–2.57) trajectories had an elevated risk for all-cause mortality. The mediation analyses showed that OHRQoL accounted for 14.6% and 11.5% of the elevated mortality risk among decreasing (indirect HR = 1.04; 95% CI = 1.01–1.08) and low-stable trajectories (indirect HR = 1.06; 95% CI = 1.01–1.11) compared to the high-stable trajectory, respectively. While modest, a moderating role of poor OHRQoL on the association between decreasing or low-stable cognitive function trajectories and all-cause mortality was observed. However, considering the uncertainty in the estimated mediation proportion, these findings should be interpreted with caution and require confirmation in future studies.</p>