Conservative treatments for early osteoarthritis (OA) of the knee included the use of non-steroid anti-inflammatory drugs (NSAIDs) and intra-articular hyaluronic acid (HA) injection. Recently, several animal studies reported that extracorporeal shockwave therapy (ESWT) demonstrated chondroprotective effects on knee OA. The present study compared the efficacy of oral NSAIDs, HA injection, and noninvasive ESWT for early OA of the knee. Forty-five patients with early knee OA were randomized into three groups. NSAIDs group received celecoxib 200 mg daily for 3 weeks. HA group received intra-articular injection of HA once a week for 3 weeks. ESWT group received ESWT for 3 sessions at bi-weekly interval. All patients were followed up for one year. Evaluations included the visual analogue scale (VAS) score, serum enzyme-linked immunosorbent assay (ELISA), plain radiography, dual-energy X-ray absorptiometry (DEXA), and magnetic resonance imaging (MRI). In addition, the functional scores were performed including, WOMAC (Western Ontario and McMaster Universities Arthritis Index) score, KOOS (knee injury and osteoarthritis outcome) score, and IKDC (International Knee Documentation Committee) score. All three groups showed significant improvement in VAS and functional scores as well as in the collected one-year follow-up data after treatments. ESWT group had better pain relief than NSAIDs and HA groups. ESWT group had better therapeutic effects in the functional scores than NSAIDs and HA groups. The bone mineral density (BMD) of proximal tibia is significantly increased after ESWT than others. In the serum ELISA, ESWT inhibited the expression of COMP in knee OA patients as compared with NSAIDs and HA groups. The parameters of MRI showed no significant differences between three groups after treatments. ESWT and intra-articular HA injection showed comparable results than NSAIDs. ESWT was superior in pain relief than HA and NSAIDs. The results demonstrated that ESWT was an effective and alternative therapy than HA and NSAIDs for early osteoarthritis of the knees.