In a randomized, controlled study, whole-body electromyostimulation (WB-EMS) was investigated as a promising alternative to conventional strength training for the treatment of knee osteoarthritis (OA). 72 overweight participants with symptomatic knee OA were randomly assigned to WB-EMS (n = 36) or a usual care control group (CG, n = 36). For seven months, the WB-EMS group received three times per fortnight a WB-EMS training, while the CG was prescribed 6x physiotherapeutic treatments. The primary outcome, change in the pain subscale of the Knee injury and Osteoarthritis Outcome Score (KOOS), significantly improved in favour of the WB-EMS group, with a mean increase of 16.7 points versus 7.0 points in the CG (absolute difference between groups 9.0 points, 95%CI 2.9 to 15.1, p = 0.004). Secondary outcomes, including the other KOOS subscales (symptoms, function in daily living, function in sports/recreational activities and quality of life), 7-day pain diary, isometric muscle strength and lower limb function (30s sit-to-stand test), were also in favour of WB-EMS. With few dropouts and no reported adverse events, WB-EMS had a participation rate of 88% ± 10%. Overall, WB-EMS was found to be effective in relieving knee pain symptoms and improving physical function in individuals with symptomatic knee OA compared to usual care treatment.