Eleven randomized controlled trials including 956 patients with knee osteoarthritis were included in this systematic review and meta-analysis comparing home-based exercise (HBE) versus center-based exercise (CBE) and HBE combined with CBE. Pooled outcomes of interest included pain, physical disability, quality of life, walking ability, lower limb muscle strength, and balance function. The analysis found no significant difference between HBE and CBE in short-term pain (p = 0.09), physical disability (p = 0.35), walking ability (p = 0.33), and lower limb muscle strength (p = 0.47). However, combining HBE with CBE yielded greater short-term benefits for pain relief (p < 0.001) and physical disability improvement (p = 0.05). These findings suggest that HBE can be a viable alternative to CBE for KOA management, but the combination of both may provide superior outcomes.