The ability to enhance both the solvent and thermal stability of semiconducting π-conjugated polymers is highly desired for various device-related applications. Herein, a series of poly(3-hexylthiophene)-stat-poly[3-(6-hydroxy)hexylthiophene] (P3HT-stat-P3HHT) statistical copolymers with thermally cross-linkable hydroxyl groups is synthesized and their crystalline structures in three different states, solvent and thermal stability for use in organic field-effect transistors (OFETs) are elucidated. Importantly, these initial P3HT-stat-P3HHT thin films in their as-cast state crystallize well in an edge-on orientation. During annealing at 150 °C, these P3HT-stat-P3HHT occur cross-linked and retain edge-on orientation with increased crystallinity and ordering. In contrast, after high-temperature annealing at 300 °C, their edge-on orientation is significantly destroyed due to the cross-linking of hydroxyl groups at melted state. The correlation between different P3HT-stat-P3HHT and their charge mobilities is scrutinized. These cross-linked P3HT-stat-P3HHT exhibit good solvent resistance property and improved thermal stability in OFETs. Conceptually, such side-chain functionalization approach to improve the stability of P3HT-stat-P3HHT can be conveniently extended to other conjugated polymers for diverse optoelectronic applications.