The study evaluated the effects of a two-week combined program of balneotherapy and aquatic exercise in thermal salt-bromine-iodine water in 66 patients with mild to moderate osteoarthritis of the knee compared to balneotherapy alone. The experimental group (EG) showed a better reduction in pain intensity of 31% versus 13% in the control group (CG) and more consistent improvements in bilateral active range of motion (AROM). Both groups showed improvements in all assessments, including WOMAC physical component scores, Lequesne Knee Algofunctional Index (LAI), and SF-12, confirmed by linear mixed effects models. Secondary outcomes included improvements in quality of life, sleep, and psychological well-being. Regression analysis showed that older age and BMI negatively influence the increase in mobility. The combined intervention significantly increases the analgesic and functional benefit of standard balneotherapy in knee OA.