In this work, the uniform Cu2O submicron-cubes were facilely synthesized by liquid phase reductionmethod. Then, the Cu2O submicron-cubes were further oxidized into Cu2O-CuO heterojunction with tunableCu2+/Cu+ ratios and CuO submicron-cubes by controlling the calcination temperature. The phasetransition period during calcination was real-time monitored by the in-situ XRD and in-situ DRIFTS. The obtained materials were investigated as the catalysts of CO oxidation. The results revealed thatthe Cu2O-CuO heterojunction catalysts performed much higher catalytic activities than the Cu2O andCuO counterparts. Because the synergistic effect of the heterojunction (Cu2+/Cu+) could increase the surfaceoxygen vacancy concentration. Furthermore, it was also found that only the Cu2O-CuO heterojunctionstructure with the appropriate Cu2+/Cu+ ratio behaved the optimum catalytic activity. The kineticstudies indicated that the apparent activation energy of CO oxidation was greatly affected by the Cu2+/Cu+ ratio. Therefore, these Cu2O-CuO submicron-cubes with heterostructure were considered as thepromising CO oxidation catalysts.