This randomized clinical trial evaluated the effectiveness of short, digital interventions in improving physical activity and pain for individuals with knee osteoarthritis. We compared a digital mindset intervention, focusing on adaptive mindsets (e.g., osteoarthritis is manageable), to a digital education intervention and a no-intervention group. 408 participants with knee osteoarthritis completed the study online in the US. The mindset intervention significantly improved mindsets compared to both other groups (P < 0.001) and increased physical activity levels more than the no-intervention group (mean = 28.6 points, P = 0.001), but pain reduction was not significant. The mindset group also showed significantly greater improvements in the perceived need for surgery, self-imposed physical limitations, fear of movement, and self-efficacy than the no-intervention and education groups. This trial demonstrates the effectiveness of brief digital interventions in educating about osteoarthritis and further highlights the additional benefits of improving mindsets to transform patients’ approach to disease management. The study was prospectively registered (ClinicalTrials.gov: NCT05698368, 2023-01-26).