Background: Pronated foot posture is associated with many clinical and biomechanical outcomes unique to medial compartment knee osteoarthritis (OA). Though shoe-worn insole treatment, including lateral wedges, is commonly studied in this patient population, their effects on the specific subgroup of people with medial knee OA and concomitant pronated feet are unknown. The purpose of this study was to evaluate whether lateral wedge insoles with custom arch support are more beneficial than lateral wedge insoles alone for knee and foot symptoms in people with medial tibiofemoral knee osteoarthritis (OA) and pronated feet. Methods: Twenty-six people with pronated feet and symptomatic medial knee OA participated in a randomized crossover study comparing five degree lateral wedge foot insoles with and without custom foot arch support. Each intervention was worn for two months, separated by a two-month washout period of no insoles wear. Main outcomes included the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain and physical function subscales, the revised short-form Foot Function Index (FFI-R) pain and stiffness subscales, and the timed stair climb test. Regression modeling was conducted to examine treatment, period, and interaction effects. Results: Twenty-two participants completed the study, and no carryover or interaction effects were observed for any outcome. Significant treatment effects were observed for the timed stair climb, with greater improvements seen with the lateral wedges with arch support. Within-condition significant improvements were observed for WOMAC pain and physical function, as well as FFI-R pain and stiffness with lateral wedges with arch support use. More adverse effects were reported with the lateral wedges alone, while more people preferred the lateral wedges with arch support overall. Conclusions: Addition of custom arch support to a standard lateral wedge insole may improve foot and knee symptoms in people with knee OA and concomitant pronated feet. These preliminary findings suggest further research evaluating the role of shoe-worn insoles for treatment of this specific sub-group of people with knee OA is warranted.