The holopelagic macroalgae of the genus Sargassum are the ecosystem engineers of a unique open-ocean rafting ecosystem in the subtropical North Atlantic and tropical Atlantic. Over the last decade, increases in biomass in the tropics and Caribbean Sea have been observed. The underlying causes of this regime shift have been difficult to discern without a baseline understanding of the drivers of Sargassum distribution. The objective of this dissertation is to fill this knowledge gap using remote and in situ observations, and coupled ocean circulation, biogeochemical, Lagrangian particle, and Sargassum physiology models. A satellite-derived Sargassum abundance climatology shows the center-of-mass of Sargassum shifting between the tropics, Caribbean, Gulf of Mexico, and Sargasso Sea throughout the year. Model experiments demonstrate that advection alone can explain up to 60% of the observed distribution at time scales shorter than two months. At longer time scales, the growth and reproductive strategy of the macroalgae interact with physical processes to drive the overall observed pattern. Sargassum populations in the Western Tropical Atlantic and Gulf of Mexico appear to exert disproportionate influence over the basin-wide distribution. One key physical process influencing both transport and growth is inertia. A novel inverse method, developed from remote sensing to determine the effective radius of Sargassum rafts, facilitates modeling inertial effects. The effective radius is on the order of 0.95 m, much closer to the size of an individual plant than that of aggregations which can span kilometers. The inclusion of inertia alters modeled distributions of Sargassum by increasing retention in the Gulf of Mexico and the Caribbean, while increasing export from the Sargasso Sea by up to 20%. Inertia acting on buoyant Sargassum rafts also leads to their increased entrainment in cyclonic eddies. These eddies propagate toward the north-west in the northern hemisphere providing transport for Sargassum from the tropics through the Caribbean to the Gulf of Mexico and leading to increased biomass due to transport into regions with better growing conditions. Sargassum biology and its interaction with ocean circulation and mesoscale features is central to improving understanding of the changes in its distribution and for prediction of costly beaching events.