A broad spectrum of physical therapy exercise programs provides symptom relief and functional benefit for patients with knee OA. Manual physical therapy, including tailored exercise programs provide relatively higher level benefit that persists to one year. It is currently unknown if there are important differences in the effects of different manual physical therapy techniques for patients with knee OA and there are virtually no studies comparing manual physical therapy and electrotherapy modalities. The aim of the study was to compare long-term results between three treatment groups (mobilization with movements [MWMs], passive joint mobilization [PJM], and electrotherapy) to determine which treatment is most effective in patients with knee OA. A single-blind randomized clinical trial with parallel design was conducted in patients with knee OA. Seventy-two consecutive patients (mean age 56.11 ± 6.80 years) with bilateral knee OA were randomly assigned to one of three treatment groups: MWMs, PJM, and electrotherapy. All groups performed an exercise program and received 12 sessions. The primary outcome measures of the functional assessment were the Western Ontario and McMaster Universities Osteoarthritis index (WOMAC) and Aggregated Locomotor Function (ALF) test scores. The secondary outcome measures were pain level, measured using a pressure algometer and a visual analogue scale (VAS), range of motion (ROM), measured using a digital goniometer, and muscle strength, evaluated with a handheld dynamometer. Patients were assessed before treatment, after treatment and after 1 year of follow-up. Patients receiving the manual physical therapy interventions consisting of either MWM or PJM demonstrated a greater decrease in VAS scores at rest, during functional activities, and during the night compared to those in the electrotherapy group from baseline to after the treatment (p < 0.05). This improvement continued at the 1-year follow-up (p < 0.05). The MWMs and PJM groups also showed significantly improved WOMAC and ALF scores, knee ROM and quadriceps muscle strength compared to those in the electrotherapy group from baseline to 1-year follow-up (p < 0.05). In the treatment of patients with knee OA, manual physical therapy consisting of either MWM or PJM provided superior benefit over electrotherapy in terms of pain level, knee ROM, quadriceps muscle strength, and functional level.