This study sought to improve the utilization of sorghum straw resources and promote the industrial production of new biomass materials. Herein, we fabricated SSP/ZnO/PVA nanocomposite films from sorghum straw powder (SSP), corn starch, polyvinyl alcohol (PVA), and nanostructured ZnO via the casting method. Then, we used response surface methodology to examine the effects of the mass concentrations of SSP, glycerol (Gly), and nanostructured ZnO, as well as the starch–PVA mass ratio on the tensile strength (TS) and water vapor permeability (WVP) of the SSP/ZnO/PVA nanocomposite films. The optimum preparation conditions were as follows: SSP mass concentration of 2.0 g/150 mL, Gly mass concentration of 2.5 g/150 mL, starch–PVA mass ratio of 6:4.5, and nanostructured ZnO mass concentration of 0.7 g/150 mL. The TS and WVP of the prepared films were 47.57% higher and 27.07% lower, respectively, than those of ZnO/PVA composite films without SSP. Scanning electron microscopy and atomic force microscopy showed that the SSP/ZnO/PVA nanocomposite films had smooth surfaces and dense cross-sections, without obvious delamination or phase separation. Fourier transform infrared spectroscopy, X-ray diffraction, and thermogravimetric analyses revealed that SSP was highly compatible with the ZnO/PVA matrix. Thus, SSP addition could improve the crystallinity, thermal stability, and matrix interactions of SSP/ZnO/PVA nanocomposite films.