The United States of America and Brazil are the world’s first and second-largest biofuels producers. The United States (U.S.) has dedicated a significant portion of agricultural land for crops to produce biodiesel, while Brazil has been using sugar cane as raw material to produce ethanol. To make the world’s top producers in global biofuel markets, various institutions in each country have played significant roles. These institutions include renewable energy legislators, bioenergy policymakers, and energy ministries of their governments. This study delineates the historical role of these institutions responsible for the sustainable development of biofuel industries in both countries. It also provides an overview of economic impacts as a result of institutional decisions. The study reveals that systematic legislations and sustainable and robust renewable energy policies of government institutions have helped the U.S. and Brazil to boost their bio-economies. As both countries intend to keep expanding their biofuel productions, the role of key government institutions is vital in the sustainability of biofuels.