Robust hydrologic models are needed to help manage water resources for healthy aquatic ecosystems and reliable water supplies for people, but there is a lack of comprehensive model comparison studies that quantify differences in streamflow predictions among model applications developed to answer management questions. We assessed differences in daily streamflow predictions by four fine-scale models and two regional-scale monthly time step models by comparing model fit statistics and bias in ecologically relevant flow statistics (ERFSs) at five sites in the Southeastern USA. Models were calibrated to different extents, including uncalibrated (level A), calibrated to a downstream site (level B), calibrated specifically for the site (level C) and calibrated for the site with adjusted precipitation and temperature inputs (level D). All models generally captured the magnitude and variability of observed streamflows at the five study sites, and increasing level of model calibration generally improved performance. All models had at least 1 of 14 ERFSs falling outside a +/−30% range of hydrologic uncertainty at every site, and ERFSs related to low flows were frequently over-predicted. Our results do not indicate that any specific hydrologic model is superior to the others evaluated at all sites and for all measures of model performance. Instead, we provide evidence that (1) model performance is as likely to be related to calibration strategy as it is to model structure and (2) simple, regional-scale models have comparable performance to the more complex, fine-scale models at a monthly time step.