The tropical Atlantic has been facing a massive proliferation of Sargassum since 2011, with severe environmental and socioeconomic impacts. The development of large-scale modeling of Sargassum transport and physiology is essential to clarify the link between Sargassum distribution and environmental conditions, and to lay the groundwork for a seasonal forecast at the scale of the tropical Atlantic basin. We developed a modeling framework based on the Nucleus for European Modelling of the Ocean (NEMO) ocean model, which integrates transport by currents and waves, and physiology of Sargassum with varying internal nutrients quota, and considers stranding at the coast. The model is initialized from basin-scale satellite observations, and performance was assessed over the year 2017. Model parameters are calibrated through the analysis of a large ensemble of simulations, and the sensitivity to forcing fields like riverine nutrient inputs, atmospheric deposition, and waves is discussed. Overall, results demonstrate the ability of the model to reproduce and forecast the seasonal cycle and large-scale distribution of Sargassum biomass.