Flexible thermoelectric (TE) materials have wide applications in fabricating portable/wearable devices owing to the advantages of being bendable, small size, and lightweight. Inorganic material–based flexible thin films have attracted much attention owing to their high TE performance. So far, developing high TE properties and environment friendly flexible thin films for practical applications is still a considerable challenge. Copper selenide (Cu2Se) is a non-toxic and low-cost material, providing relatively safe TE modules for thin film devices. In this work, Cu2Se-based thin films with single crystal phase have been fabricated successfully at a flexible substrate by an efficient layer-by-layer combination reaction method. By optimizing the composition, a high power factor of 5.3 μWcm−1K−2 and dimensionless figure of merit value of 0.35 with low thermal conductivity are achieved at room temperature. Through bending tests, it has been shown that the prepared thin films possess good flexibility and the designed flexible device displays stable output power, which demonstrates the potential of inorganic TE materials to be mountable on flexible/wearable substrates for energy harvesting and management devices.