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Limitations of plain radiographs may contribute to poor sensitivity in the detection of knee osteoarthritis and poor correlation with pain and physical function. Three‐dimensional (3D) joint space width (JSW), measured from weight‐bearing computed tomography (CT) images, may yield a more accurate correlation with patients' symptoms. We assessed the cross‐sectional association between 3D JSW and self‐reported pain and physical function. Five hundred twenty eight knees (57% women) were analyzed from Multicenter Osteoarthritis Study participants. An upright weight‐bearing CT scanner was used to acquire bilateral, weight‐bearing, fixed‐flexion images of the knees. A 3D dataset was reconstructed from cone beam projections and JSW was calculated across the joint surface. The percentages of the apposed medial tibiofemoral joint surface with JSW less than 2.0 and 2.5 mm, respectively, were calculated. Pain and physical function were measured using Western Ontario and McMaster Universities Osteoarthritis Index. Participants who reported greater pain severity tended to have a greater joint area with JSW less than 2.0 mm (P =.07 for the highest vs the lowest tertile). Participants who reported greater functional limitations had a greater joint area with JSW less than 2.0 mm (P =.02 for the highest vs the lowest tertile). There appears to be an association between the medial tibiofemoral area with JSW less than 2.0 mm and pain and physical function. [ABSTRACT FROM AUTHOR]