Diabetes mellitus (DM) is a recognized risk factor for dementia, and increasing evidence shows that tooth loss is associated with cognitive impairment and dementia. However, the effect of the co-occurrence of DM and edentulism on cognitive decline is understudied. This 12-y cohort study aimed to assess the effect of the co-occurrence of DM and edentulism on cognitive decline and examine whether the effect differs by age group. Data were drawn from the 2006 to 2018 Health and Retirement Study. The study sample included 5,440 older adults aged 65 to 74 y, 3,300 aged 75 to 84 y, and 1,208 aged 85 y or older. Linear mixed-effect regression was employed to model the rates of cognitive decline stratified by age cohorts. Compared with their counterparts with neither DM nor edentulism at baseline, older adults aged 65 to 74 y (β = −1.12; 95% confidence interval [CI], −1.56 to −0.65; P < 0.001) and those aged 75 to 84 y with both conditions (β = −1.35; 95% CI, −2.09 to −0.61; P < 0.001) had a worse cognitive function. For the rate of cognitive decline, compared to those with neither condition from the same age cohort, older adults aged 65 to 74 y with both conditions declined at a higher rate (β = −0.15; 95% CI, −0.20 to −0.10; P < 0.001). Having DM alone led to an accelerated cognitive decline in older adults aged 65 to 74 y (β = −0.09; 95% CI, −0.13 to −0.05; P < 0.001); having edentulism alone led to an accelerated decline in older adults aged 65 to 74 y (β = −0.13; 95% CI, −0.17 to −0.08; P < 0.001) and older adults aged 75 to 84 (β = −0.10; 95% CI, −0.17 to −0.03; P < 0.01). Our study finds the co-occurrence of DM and edentulism led to a worse cognitive function and a faster cognitive decline in older adults aged 65 to 74 y.