Objective: The prevalence of symptomatic knee osteoarthritis (OA) has been increasing over the past several decades in the US, concurrent with an aging population and the growing obesity epidemic. We quantify the impact of these factors on the number of persons with symptomatic knee OA in the early decades of the 21st century.Methods: We calculated the prevalence of clinically diagnosed symptomatic knee OA from the National Health Interview Survey 2007–2008 and derived the proportion with advanced disease (defined as Kellgren/Lawrence grade 3 or 4) using the Osteoarthritis Policy Model, a validated simulation model of knee OA. Incorporating contemporary obesity rates and population estimates, we calculated the number of persons living with symptomatic knee OA.Results: We estimate that approximately 14 million persons had symptomatic knee OA, with advanced OA comprising more than half of those cases. This includes more than 3 million persons of racial/ethnic minorities (African American, Hispanic, and other). Adults younger than 45 years of age represented nearly 2 million cases of symptomatic knee OA and individuals between 45 and 65 years of age comprised 6 million more cases.Conclusion: More than half of all persons with symptomatic knee OA are younger than 65 years of age. As many of these younger persons will live for 3 decades or more, there is substantially more time for greater disability to occur, and policymakers should anticipate health care utilization for knee OA to increase in the upcoming decades. These data emphasize the need for the deployment of innovative prevention and treatment strategies for knee OA, especially among younger persons.