The thermoelectric (TE) properties of n-type polycrystalline Yb0.5Ba7.5Ga16Ge30 bulks can be optimized by high-pressure and high-temperature (HPHT) sintering. After HPHT sintering, abundant nanograins are randomly distributed in the sample. Grains are refined by HPHT, with the grains being smaller with higher pressure. In comparison with the arc-melted sample, the samples obtained by quenching under high pressure possess a great number of nanograins and lattice structural disorders. Lower thermal conductivity is benefited by our deliberately engineered microstructures via HPHT, and the minimum thermal conductivity is 0.86 W m-1 K-1 at 773 K. The thermal conductivity and electrical properties are optimized simultaneously by raising the reactive sintering pressure. In comparison with the arc-melted sample (0.56), a maximum zT value of 1.13 at 773 K is obtained for the Yb0.5Ba7.5Ga16Ge30 sample fabricated at 5 GPa. This demonstrates that HPHT provides an effective strategy to improve TE performance through simultaneously enhancing electrical and thermal transport properties and should be applicable to other thermoelectric materials.