Deficits in voluntary activation of the quadriceps muscle are characteristic of knee osteoarthritis (OA), contributing to the quadriceps weakness that is also a hallmark of the disease. The mechanisms underlying this central activation deficit (CAD) are unknown, although cortical mechanisms may be involved. Here, we utilize transcranial magnetic stimulation (TMS) to assess corticospinal and intracortical excitability in patients with knee OA and in a comparably aged group of healthy older adults, to quantify group differences, and to examine associations between TMS measures and pain, quadriceps strength, and CAD. Seventeen patients with knee OA and 20 healthy controls completed testing. Motor evoked potentials were measured at the quadriceps by superficial electromyographic recordings. Corticospinal excitability was assessed by measuring resting motor threshold (RMT) to TMS stimulation of the quadriceps representation at primary motor cortex, and intracortical excitability was assessed via paired-pulse paradigms for short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF). No statistically significant differences between patients with knee OA and healthy controls were found for RMT, SICI or ICF measures (p > 0.05). For patients with knee OA, there were significant associations observed between pain and RMT, as well as between pain and ICF. No associations were observed between CAD and measures of corticospinal or intracortical excitability. These data suggest against direct involvement of corticospinal or intracortical pathways within primary motor cortex in the mechanisms of CAD. However, pain is implicated in the neural mechanisms of quadriceps motor control in patients with knee OA.