A quantum mechanical/molecular mechanical minimum free energy path (QM/MM-MFEP) method was developed to calculate the redox free energies of large systems in solution with greatly enhanced efficiency for conformation sampling. The QM/MM-MFEP method describes the thermodynamics of a system on the potential of mean force surface of the solute degrees of freedom. The molecular dynamics (MD) sampling is only carried out with the QM subsystem fixed. It thus avoids "on-the-fly" QM calculations and thus overcomes the high computational cost in the direct QM/MM MD sampling. In the applications to two metal complexes in aqueous solution, the new QM/MM-MFEP method yielded redox free energies in good agreement with those calculated from the direct QM/MM MD method. Two larger biologically important redox molecules, lumichrome and riboflavin, were further investigated to demonstrate the efficiency of the method. The enhanced efficiency and uncompromised accuracy are especially significant for biochemical systems. The QM/MM-MFEP method thus provides an efficient approach to free energy simulation of complex electron transfer reactions.