We discuss the strategies for the calculation of quantum transport in disordered graphene systems from the quasi-one-dimensional to the two-dimensional limit. To this end, we employ real- and momentum-space versions of the non-equilibrium Green’s function formalism along with acceleration algorithms that can overcome computational limitations when dealing with two-terminal devices of dimensions that range from the nano- to the micro-scale. We apply this formalism for the case of rectangular graphene samples with a finite concentration of single-vacancy defects and discuss the resulting localization regimes.