The risk of fatigue damage within the L5-S1 spinal disc was calculated for a sample of 52 individuals with unilateral limb loss (26 transtibial; 26 transfemoral) and 26 uninjured controls using a non-linear multi-axial fatigue model of the spine motion segments. Time to complete damage was calculated for each participant and walking pace; the influences of walking activity were determined by varying daily step counts. Assuming similar activity across groups (10,000 steps per day), times to failure were not different between persons with and without limb loss (50 [23] vs. 46 [24] years, respectively); walking faster was associated with shorter times to failure. Greater daily step counts similarly decreased time to failure in all groups. While such a similarity in fatigue damage evolution does not necessarily downplay the role of biomechanical factors, it may highlight the important influences of psychosocial factors in the development of low back pain in persons with limb loss. Nevertheless, with additional work to include activities beyond walking, computational damage models can provide a predictive platform for evaluating specific clinical interventions (e.g., behavior modification, movement retraining, prosthetic devices) that are ultimately intended to mitigate physical risk factors for low back pain following limb loss.