Osteoarthritis is the most common disabling joint disease throughout the world, and the effect of therapy on its course is still unsatisfactory in clinical practice. Recent studies have shown that mesenchymal stem cell (MSC)- derived exosomes can promote cartilage repair and regeneration in osteoarthritis, indicating that these exosomes could be a novel and promising strategy for treating osteoarthritis. This study investigated whether low-intensity pulsed ultrasound (LIPUS) enhances the effects of bone marrow MSC (BMSC)-derived exosomes on cartilage regeneration in osteoarthritis and examined the underlying mechanism. Our results revealed that BMSC-derived exosomes display the typical morphological features of exosomes. LIPUS-mediated BMSC-derived exosomes promoted cartilage regeneration, increased chondrocyte proliferation and extracellular matrix synthesis, suppressed inflammation, and inhibited the interleukin (IL)-1β-induced activation of the nuclear factor kappa B (NFκB) pathway. In brief, LIPUS enhances the promoting effects of BMSC-derived exosomes on osteoarthritic cartilage regeneration, mainly by strengthening the inhibition of inflammation and further enhancing chondrocyte proliferation and cartilage matrix synthesis. The underlying mechanism could be related to the inhibition of the IL-1β-induced activation of the NF-κB pathway.