P-type CuO films were prepared by solution processed method and annealed at 300 °C with the annealing time of 10, 30, 60, 90, and 120 min, respectively. X-ray diffraction and atomic force microscopy results reveal that the CuO film microstructures, crystallinity and grain size can be modified by annealing time. The CuO film annealed at 30 min exhibits the optimal crystalline quality. The annealing time shows a significant impact on the mobility, Ion/Ioff ratio and subthreshold swing (SS) values of the prepared CuO thin-film transistors (TFTs). By changing the annealing time, the mobility increases from 1.6 × 10−4 to 1.2 × 10−2 cm2 V−1 s−1 while the Ion/Ioff ratio increases from 2 × 103 to 2 × 104. Moreover, the transistor with annealing time of 30 min achieves the optimal field-effect mobility (1.2 × 10−2 cm2 V−1 s−1), Ion/Ioff ratio (2 × 104), and SS value (6.3 Vdec−1). It can be ascribed to fewer grain boundaries and better interface contact of the CuO film, which will reduce the densities of trapping centers and scattering centers. This work demonstrates that the crystalline quality and microstructures of CuO film and TFTs performance can be modulated by annealing time.