This study examined the relationship between cognitive change and instrumental activities of daily living (IADL) in a large, national, population-based sample. Cognitive change was assessed via verbal fluency, word list learning (WLL), and word list delayed recall (WLD). Incident cognitive impairment was defined by change in Six-Item Screener (SIS) status over a period of 10 years. Impaired IADL was defined as self-reported difficulty or needing assistance performing any IADL at Year 10. A one-word decrease in WLL over a 10-year span increased the odds of impaired IADL by 16% (95% CI 1.08–1.24) and incident cognitive impairment increased the odds of impaired IADL by 59% (95% CI 1.36–1.85) when adjusting for demographic factors, health-related behaviors, vascular risk factors and disease, and depressive symptoms. Cognitive change most strongly predicted impairment in managing finances (OR 2.47, 95% CI 2.04–3.00) and driving (OR 2.06, 95% CI 1.73–2.44).