We prove global well-posedness of the fifth-order Korteweg-de Vries equation on the real line for initial data in $H^{-1}(mathbb{R})$. By comparison, the optimal regularity for well-posedness on the torus is known to be $L^2(mathbb{R}/mathbb{Z})$. In order to prove this result, we develop a strategy for integrating the local smoothing effect into the method of commuting flows introduced previously in the context of KdV. It is this synthesis that allows us to go beyond the known threshold on the torus.