Polypharmacy, a common condition among the older population, is associated with adverse outcomes, including higher mortality, falls and hospitalization rates, adverse drug reactions, drug–drug interactions, medication nonadherence, and consequently increased healthcare costs. Background/Objectives: This study aims to explore the prevalence of polypharmacy and its associated factors among older adults across 27 European countries and Israel. Methods: In this cross-sectional analysis, we used data from participants aged 65 years or older from Wave 9 of the Survey of Health, Aging, and Retirement in Europe (SHARE) database. The variables studied were classified into the following categories: sociodemographic, behavioral factors, physical functioning, physical health, mental health, and living conditions. Results: Our results showed an overall prevalence of polypharmacy of 36.2%, ranging from 25.0 to 51.8%. Slovenia, Greece, and Switzerland were the countries with the lowest prevalence, whereas Portugal, Israel, and Poland were the countries where the prevalence of polypharmacy was the highest. Polypharmacy was shown to be associated with variables from all categories. Conclusions: Polypharmacy is a highly prevalent condition in the older population. Identification of variables associated with polypharmacy, such as those identified in this study, is important to identify and monitor older groups, which are most vulnerable to polypharmacy. Interventions designed to reduce polypharmacy should consider these associations.