The numerical simulation of rarefied gas mixtures with disparate mass and concentration is a huge research challenge. Based on our recent kinetic modeling for monatomic gas mixture flows, this problem is tackled by the general synthetic iterative scheme (GSIS), where the mesoscopic kinetic and macroscopic synthetic equations are alternately solved by the finite-volume discrete velocity method. Three important features of GSIS are highlighted. First, the synthetic equations are precisely derived from the kinetic equation, naturally reducing to the Navier-Stokes equations in the continuum flow regime; in other flow regimes, the kinetic equation provides high-order closure of the constitutive relations to capture the rarefaction effects. Second, these synthetic equations, which can be solved quickly, help to adjust the kinetic system to relax rapidly toward the steady state. Furthermore, in such a two-way coupling, the constraint on the spatial cell size is relieved. Third, the linear Fourier stability analysis demonstrates that the error decay rate in GSIS is smaller than 0.5 for various combinations of mass, concentration and viscosity ratios, such that the error can be reduced by three orders of magnitude after 10 iterations. The efficiency and accuracy of GSIS are demonstrated through several challenging cases covering a wide range of mass ratio, species concentration, and flow speed.