Chronic illness has a significant effect on quality of life, and a critical measure of health outcomes. Correlations between pain, depressive symptoms, fatigue, and physical function and their direct and indirect effects on quality of life were determined among 200 Thai older population with knee osteoarthritis using the Numeric Rating Scale, the Multidimensional Assessment of Fatigue, and the Thai Geriatric Depression Scale‐15. Physical function was investigated by using the Timed Up and Go test. Path analysis revealed significant negative direct paths from pain, depressive symptoms, fatigue, and Timed Up and Go test results to quality of life. Pain, fatigue, and the Timed Up and Go test results had indirect effects on quality of life, while depressive symptoms had no indirect effect on quality of life. Increases in pain, depressive symptoms, fatigue, and Timed Up and Go test results were associated with reductions in quality of life. An understanding of the complex relationship among these variables is beneficial for designing an appropriate intervention for improving quality of life among older people with knee osteoarthritis.