Objective: To investigate the clinical efficacy of Yang’s tendon-regulating manipulation combined with innovative nine-needle therapy in treating early-to-mid-stage knee osteoarthritis (KOA). Methods: A total of 300 KOA patients were randomly divided into a treatment group and a control group, with 150 patients in each. The control group received Yang’s tendon-regulating manipulation combined with filiform needle acupuncture, while the treatment group received Yang’s tendon-regulating manipulation combined with innovative nine-needle therapy, both for a period of ten days. Pain Visual Analog Scale (VAS) scores, Present Pain Intensity (PPI) scores, and Lysholm knee function scores were measured in both groups before and after treatment. Results: After treatment, the efficacy rate in the treatment group was 90.67%, significantly higher than the 70.57% in the control group (P<0.05). The VAS scores of the treatment group were superior to those of the control group (P<0.05); similarly, PPI scores and Lysholm knee function scores in the treatment group were significantly better than those in the control group (P<0.05). Conclusion: The combination of Yang’s tendon-regulating manipulation and innovative nine-needle therapy demonstrates significant efficacy, effectively alleviating pain in KOA patients, enhancing knee joint function, accelerating recovery, and improving quality of life.