Background: The use of physical therapy modalities, especially high intensity laser therapy (HILT), for individuals with knee osteoarthritis (KOA) is still controversial. Objective: To compare the effects of HILT to other physical therapy modalities on symptoms and function in individuals with KOA. Methods: Six databases (PubMed, Embase, Cochrane Library, Web of Science, EBSCO, and PEDro) were searched in March 2022. Included studies were randomized controlled trials involving HILT conducted on individuals with KOA. The end-trial weighted mean difference (WMD) and standard deviations (SD) with 95% confidence intervals (CI) were analyzed. Results: Ten studies with 580 participants were obtained, of which nine were included in the final network meta-analysis. In terms of relieving pain, HILT demonstrated the highest probability of being among the most effective treatments, with surface under the cumulative ranking (SUCRA) = 100%, and compared to a control (placebo laser or exercise or a combination of both) on the visual analog scale (VAS) for pain it demonstrated significant benefits (WMD 1.66, 95% CI 1.48–1.84). For improving self-reported function, as measured by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) total scores, the HILT SUCRA value led with 98.9%. When individuals with KOA were treated by HILT, the improvement in stiffness was statistically significant (WMD 0.78, 95% CI 0.52–1.04) but the amount of improvement was smaller than the minimal clinically important difference (MCID). Conclusion: The current evidence suggests that HILT may be more effective than other physical therapy modalities for improving pain and function in individuals with KOA. For improving stiffness, however, it may not be clinically effective. Systematic review registration: [https://www.researchregistry.com], identifier .