Ecosystems dominated by big sagebrush, Artemisia tridentata Nuttall (Asteraceae), which are the most widespread ecosystems in semiarid western North America, have been affected by land use practices and invasive species. Loss of big sagebrush and the decline of associated species, such as greater sage-grouse, are a concern to land managers and conservationists. However, big sagebrush regeneration remains difficult to achieve by restoration and reclamation efforts and there is no regeneration simulation model available. We present here the first process-based, daily time-step, simulation model to predict yearly big sagebrush regeneration including relevant germination and seedling responses to abiotic factors. We estimated values, uncertainty, and importance of 27 model parameters using a total of 1435 site-years of observation. Our model explained 74% of variability of number of years with successful regeneration at 46 sites. It also achieved 60% overall accuracy predicting yearly regeneration success/failure. Our results identify specific future research needed to improve our understanding of big sagebrush regeneration, including data at the subspecies level and improved parameter estimates for start of seed dispersal, modified wet thermal-time model of germination, and soil water potential influences. We found that relationships between big sagebrush regeneration and climate conditions were site specific, varying across the distribution of big sagebrush. This indicates that statistical models based on climate are unsuitable for understanding range-wide regeneration patterns or for assessing the potential consequences of changing climate on sagebrush regeneration and underscores the value of this process-based model. We used our model to predict potential regeneration across the range of sagebrush ecosystems in the western United States, which confirmed that seedling survival is a limiting factor, whereas germination is not. Our results also suggested that modeled regeneration suitability is necessary but not sufficient to explain sagebrush presence. We conclude that future assessment of big sagebrush responses to climate change will need to account for responses of regenerative stages using a process-based understanding, such as provided by our model.