Objective: To investigate the 2-year association of varus knee thrust observed during walking to the odds of worsening Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) knee pain in older adults with or at risk of osteoarthritis (OA). Methods: Video recordings of self-paced walking trials of Multicenter Osteoarthritis Study participants were assessed for the presence of varus thrust at baseline. Knee pain was assessed using the WOMAC questionnaire at baseline and at 2 years. Logistic regression was used to estimate the odds of worsening knee pain (defined as either any increase in WOMAC score or as clinically important worsening), adjusting for age, sex, race, body mass index, clinic site, gait speed, and static knee alignment. Analyses were repeated, stratified by baseline radiographic OA status and among the subset of knees without baseline WOMAC pain. Results: A total of 1,623 participants contributed 3,204 knees. Varus thrust was observed in 31.5% of knees. Knees with varus thrust had 1.44 times (95% confidence interval [95% CI] 1.19–1.73) the odds of any worsening and 1.37 times (95% CI 1.11–1.69) the odds of clinically important worsening WOMAC pain compared to knees without thrust. Knees with thrust without baseline WOMAC pain had 2.01 times (95% CI 1.47–2.74) the odds of incident total pain. Conclusion: Results indicate that varus thrust is a risk factor for worsening and incident knee pain. Targeting varus thrust through noninvasive therapies could prevent development or worsening of knee pain in older adults with or at risk for knee OA.