We determined whether more adverse calf muscle characteristics and poorer peripheral nerve function were associated with impairments in self-perceived physical functioning and walking ability in persons with lower extremity peripheral artery disease (PAD). Participants included 462 persons with PAD; measures included the ankle-brachial index (ABI), medical history, electrophysiologic characteristics of nerves, and computed tomography of calf muscle. Self-perceived physical functioning and walking ability were assessed using the 36-Item Short Form Health Survey (SF-36) and the Walking Impairment Questionnaire (WIQ). Results were adjusted for age, sex, race, ABI, body mass index, comorbidities, and other confounders. Lower calf muscle area was associated with a poorer SF-36 physical function (PF) score (overall p-trend < 0.001, 33.76 PF score for the lowest quartile versus 59.74 for the highest, pairwise p < 0.001) and a poorer WIQ walking distance score (p-trend = 0.001, 29.71 WIQ score for the lowest quartile versus 48.43 for the highest, pairwise p < 0.001). Higher calf muscle percent fat was associated with a poorer SF-36 PF score (p-trend < 0.001, 53.76 PF score for the lowest quartile versus 40.28 for the highest, pairwise p = 0.009). Slower peroneal nerve conduction velocity was associated with a poorer WIQ speed score ( p-trend = 0.023, 30.49 WIQ score for the lowest quartile versus 40.48 for the highest, pairwise p = 0.031). In summary, adverse calf muscle characteristics and poorer peripheral nerve function are associated significantly and independently with impairments in self-perceived physical functioning and walking ability in PAD persons.