The debate over the optimal orientation of Ag2Se thin films and its influence on thermoelectric performance remains ongoing. Here, we report a wet-chemical selenization-based anisotropy optimization technique to control the in-plane orientation of the Ag2Se thin film, steering it away from (002) nearly parallel planes that hinder charge carrier mobility. This approach enables us to achieve an impressive power factor of 30.8 μW cm−1 K−2 at 343 K. The as-fabricated Ag2Se thin film demonstrates remarkable durability, retaining over 90% of its power factor after six months of air exposure, and outstanding flexibility, with performance variation staying within 5% after 2000 bending cycles at a 5 mm radius. These attributes are attributed to the controlled film thickness, crystallinity, and strong adhesion to the polyimide substrate. Additionally, the as-assembled slotted thermoelectric device delivers an output power of 0.58 μW and a competitive power density of 807 μW cm−2 at a temperature difference of 20 K, alongside a high normalized power density of 1.8 μW cm−2 K−2, highlighting its potential for practical application. This study provides valuable insights into the design of high-performance, highly flexible thermoelectric thin films for real-world applications. The authors report a wet-chemical selenization-based anisotropy optimization to control the orientation of the Ag2Se thin film, achieving a power factor of 30.8 μW cm−1 K−2 in the thin film and a normalized power density of 1.8 μW cm−2 K−2 in the device.