Knee joint osteoarthritis is a chronic disease that affects the health in aging population. We explore a minimally invasive surgery combining the use of ultrasonic drug penetration to treat early stage of knee joint osteoarthritis. In total, 75 patients were participated in acupotomy therapy and ultrasonic drug penetration to treat joint osteoarthritis. The WOMAC (the Western Ontario and McMaster Universities Osteoarthritis Index) scores were used to assess the performance. There was a significant difference in the WOMAC score between the two groups of patients (P < 0.05). The total performance rate was about 86.4% and 50% in experiment and control groups. The combination of acupotomy therapy and ultrasonic drug penetration has demonstrated to be effective and promising to treat knee joint osteoarthritis.