The effect of thermally generated equilibrium carrier distribution on the vacancy generation, recombination, and mobility in a semiconductor heterostructure with an undoped quantum well is studied. A different rate of thermally generated equilibrium carriers in layers with different band gaps at annealing temperatures forms a charge-carrier density gradient along a heterostructure. The nonuniform spatial distribution of charged vacancy concentration that appears as a result of strong dependence in the vacancy formation rate on the local charge-carrier density is revealed. A model of vacancy-mediated diffusion at high temperatures typical for post-growth annealing that takes into account this effect and dynamics of nonequilibrium vacancy concentration is developed. The change of atomic diffusivity rate in time that follows on the of spatial vacancy distribution dynamics in a model heterostructure with quantum wells during a high-temperature annealing at fixed temperatures is demonstrated by computational modeling.