© 2016, American College of Rheumatology. Objective Symptomatic knee osteoarthritis (OA) is a condition commonly associated with increased pain, disability, and functional limitations. Given the poor correspondence between radiographic evidence and clinical pain, central sensitization has been implicated as a potential mechanism underlying pain facilitation in knee OA. Sex may be a moderator of centrally mediated changes in knee OA pain; however, few studies have systematically assessed this. Therefore, the aim of this study was to examine differences in peripheral and central sensitization in men and women with symptomatic knee OA, as well as to determine whether these differences vary across age (middle age versus older age). Methods Participants (n = 288) between the ages of 45 and 85 years completed a battery of quantitative sensory pain procedures assessing sensitivity to contact heat, cold pressor, mechanical pressure, and punctate stimuli. Differences in temporal summation (TS) were examined, as well as measures of clinical pain and functional performance. Results When compared to men, women exhibited greater sensitivity to multiple pain modalities (i.e., lower heat, cold, pressure thresholds/tolerances, greater TS of pain); however, there were no sex differences in clinical pain, with the exception of greater widespread pain observed in women. Although there were select age-related differences in pain sensitivity, sex differences in pain varied minimally across the age cohort. Conclusion Overall, these findings provide evidence for greater overall sensitivity to experimental pain in women with symptomatic knee OA compared to men, suggesting that enhanced central sensitivity may be an important contributor to pain in this group.