Hydrological modeling is nowadays critical for evaluating the status, past trends, and future perspectives of water availability at the global, regional, and local scales. The Iberian Peninsula is registering more frequent and severe droughts and water scarcity caused not only by extreme meteorological events, but also by increased demand for water for urban, industrial, and agricultural supplies. Better simulation models are thus needed for accurately quantifying the availability of local water resources. In this study, the natural flow regime in different watersheds of the Iberian Peninsula was simulated using the process-based, fully distributed, MOHID-Land model from 1979 to 2013. Streamflow results were compared with measurements at 73 hydrometric stations not influenced by reservoirs, and with the data available in the management plans of each hydrographic region. The results showed a high dispersion of the goodness-of-fit indicators, with the coefficient of determination (R2) ranging between 0 and 0.91, and the modeling efficiency (NSE) being higher than 0.35 at only 22 (calibration) and 28 (validation) hydrometric stations. Considering the scale of application, results were acceptable but evidenced the difficulties in simulating streamflow in watersheds using a coarse resolution. As such, this paper further deals with the difficulties and challenges of the adopted modeling approach. Nevertheless, this study constitutes a further step towards the more accurate assessment of water resources availability at the Iberian Peninsula scale using process-based modeling.