Background: Previous studies have reported on the higher risk of functional decline among older patients with cancer. However, few have focused on factors of functional decline in older persons with cancer and are mainly hospital-based and focus on consequences of cancer treatment. The aim of the study was to identify determinants of functional decline in older subjects with cancer in a population-based study. Methods: Using cancer registries, we identified older subjects (age ≥ 65 years) with cancer in three prospective cohort studies from Gironde, a French department. Functional status was measured using the Instrumental Activities of Daily Living (IADL) and the basic Activities of Daily Living (ADL) scales, and functional decline was measured between cancer pre- and post-diagnosis visits. Studied variables were demographic and socioeconomic (age at diagnosis, sex, living alone, education), cancer-related (stage at diagnosis, treatment received), smoking status, health-related (polypharmacy, depressive symptomatology), and geriatric-specific (cognitive impairment or dementia). Analyses were performed using logistic regression models. Results: Age (≥85 years), cognitive impairment or dementia, and advanced stage at diagnosis were associated with a higher risk of ADL limitations, whether considering death or not. Age (≥85 years), education and polypharmacy were associated with a higher risk of ADL and/or IADL limitations. Conclusions: We identified factors that could impact on ADL and/or IADL limitations in older patients with cancer. The information on these determinants is useful in clinical settings to identify patients with cancer at high risk of functional decline.