Both structural and clinical changes can signify knee osteoarthritis progression; however, these changes are not always concurrent. A better understanding of mechanical factors associated with progression and whether they differ for structural versus clinical outcomes could lead to improved conservative management. This study examined baseline gait differences between progression and no progression groups defined at an average of 7-year follow-up using 2 different outcomes indicative of knee osteoarthritis progression: radiographic medial joint space narrowing and total knee arthroplasty. Of 49 individuals with knee osteoarthritis who underwent baseline gait analysis, 32 progressed and 17 did not progress using the radiographic outcome, while 13 progressed and 36 did not progress using the arthroplasty outcome. Key knee moment and electromyography waveform features were extracted using principal component analysis, and confidence intervals were used to examine between-group differences in these metrics. Those who progressed using the arthroplasty outcome had prolonged rectus femoris and lateral hamstrings muscle activation compared with the no arthroplasty group. Those with radiographic progression had greater mid-stance internal knee rotation moments compared with the no radiographic progression group. These results provide preliminary evidence for the role of prolonged muscle activation in total knee arthroplasty, while radiographic changes may be related to loading magnitude.