<p>Chronic kidney disease (CKD) and stroke independently accelerate cognitive decline; however, there is sparse evidence on their co-occurrence and additive effects. We examined the association of CKD and post-stroke cognitive decline. This population-based retrospective cohort study linked the Korean National Health Insurance Service and Long-Term Care Insurance databases (LTCI). Among 359,572 LTCI applicants with repeated standardized cognitive assessments (cognitive function equivalent score), participants were classified by baseline CKD status and timing of neurological conditions. Multivariable linear and multinomial logistic regression models were estimated to assess the rate and odds of cognitive decline. We also examined the interactions between CKD and stroke. CKD alone modestly accelerated cognitive decline (<i>β</i> = 0.19; 95% CI, 0.11 to 0.27). Pre-existing stroke alone was not associated with decline; however, the addition of CKD increased the effect (<i>β</i> = 1.12; 95% CI, 0.50 to 1.75). Incident stroke alone also accelerated decline (<i>β</i> = 0.73; 95% CI, 0.47 to 1.00), and co-occurrence with CKD produced a numerically greater effect (<i>β</i> = 0.98; 95% CI, 0.59 to 1.37; adjusted odds ratio = 1.69; 95% CI, 1.45 to 1.97). Formal interaction testing showed a significant positive CKD × pre-existing stroke interaction on the continuous scale (<i>β</i> = 1.01; 95% CI, 0.27 to 1.75; <i>p</i> = 0.007). In contrast, interactions for incident and recurrent stroke, the odds-ratio scale, and the additive scale were directionally consistent but not statistically significant. In secondary analyses, CKD × dementia and CKD × Parkinson’s disease interactions were null or negative. CKD was associated with greater functional cognitive decline following stroke. In conclusion, these findings suggest a possible interaction in which pre-existing CKD is associated with greater post-stroke cognitive decline; however, the strength of the interaction was not consistent across analytical approaches.</p>