This systematic review and meta-analysis included 35 randomized controlled trials (RCTs) with 3,348 patients diagnosed with knee osteoarthritis (OA), comparing intra-articular corticosteroid (CS) injections with hyaluronic acid (HA) and platelet-rich plasma (PRP). Pooled outcomes assessed improvements in pain and function using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and Visual Analog Scale (VAS) scores at different follow-up intervals up to 12 months. The analysis found that CS and HA provided similar WOMAC improvements, though HA showed slightly better VAS pain relief at long-term follow-up (P = 0.011) without reaching clinical significance. PRP demonstrated superior WOMAC improvements compared to CS at short- (P = 0.002), mid- (P < 0.001), and long-term (P < 0.001) follow-ups, exceeding the minimal clinically important difference (MCID). PRP also significantly improved VAS pain scores at mid- (P < 0.001, exceeding MCID) and long-term (P = 0.023) follow-ups. These findings suggest that while CS and HA offer short-term relief, PRP provides superior and clinically relevant benefits for knee OA patients over time.