A number of non-operative treatment options are commonly prescribed for patients presenting with degenerative osteoarthritis of the knee, where surgery is not yet recommended. However, there is a paucity of studies evaluating the comparative effectiveness of these treatment options to best inform both patients and providers. This study examined the comparative effectiveness of a home exercise program versus bracing or a combination of the two (brace-only, exercise-only, and brace and exercise cohorts) on the following: 1) objective functional measures (quadriceps muscle strength, Self-Paced Walk Test [SPWT], and Timed "Up & Go" [TUG] Test); 2) subjective functional measures (Lower Extremity Function Scale [LEFS] and Health Survey [VR-12] outcomes); 3) pain using Visual Analog Scale [VAS-10]; 4) patient metrics (patient treatment preference, perceptions, and compliance); and 5) progression to total knee arthroplasty (TKA) over a 12-week period. Subjects exhibited significant improvements from baseline on all measures regardless of group assignment; however, the only significant difference between groups was the larger improvement in pain scores between the brace-only and the exercise-only cohorts (p = 0.022). The brace-only regimen may be more efficacious; however, larger studies are needed to confirm this. These findings suggest that patients who are provided with either treatment option may be able to achieve a better quality of life and return to activity that may delay an elective joint arthroplasty surgery.