Perovskite manganite Ca0.9R0.1MnO3-δ (R = Dy, Yb) ceramics have been synthesized by a traditional solid-state reaction with multicalcination processes. A heterogeneous microstructure including large and small micrometer-sized grains, coherent interfaces, and oxygen defects has been formed with optimized calcination time. The carrier concentration of the third-calcined samples is enhanced approximately 3 times compared with those synthesized through conventional methods. Thus, the electrical resistivity of the third-calcined Ca0.9R0.1MnO3-δ (R = Dy, Yb) ceramic samples obviously decreases, leading to a higher power factor. Additionally, the thermal conductivity is also reduced by multiscale scattering of the heterogeneous structure. The lowest lattice thermal conductivities of Dy- or Yb-doped samples are 1.24 and 1.22 W m-1 K-1, respectively. Thus, the high thermoelectric performance for Ca0.9R0.1MnO3-δ (R = Dy, Yb) has been achieved by the multicalcination process. The highest figure of merit is almost 30% higher than that of the first-calcined samples. Therefore, a heterogeneous microstructure formed by optimized multicalcination can effectively optimize the thermoelectric performance of oxides.