To better understand the mechanisms of bone stress injuries (BSI) in metatarsals, we developed a program that modifies finite element (FE) models of metatarsals to mimic progressive fatigue damage through microdamage accumulation. Twenty-two human metatarsals were imaged using computed tomography (CT) and then cyclically loaded in uniaxial compression until failure. CT images were used to generate specimen-specific FE models and a custom program was developed to iteratively simulate cyclic loading and microdamage accumulation associated with mechanical fatigue. Probability was incorporated into microdamage accumulation through a Weibull distribution Fatigue life estimates were significantly affected by 1) the Weibull scatter variable, m, and 2) if damage occurred before or after yielding. Our findings show that the stiffness and displacement curves of the progressive damage model accurately represent those curves of the experimental data. This research is significant because it helps us better understand fatigue life and damage accumulation of bones in response to physical activity and contributes to prediction of BSI in humans.