Tuning the phase separation within the active layer morphology is of great importance for enhancing the device performance of organic solar cells (OSCs), especially for all-small-molecule OSCs (ASM-OSCs). Herein, we demonstrate that an optimal phase separation could be achieved through thermal annealing (TA) for two small-molecule acceptors, F-2Cl- and FO-2Cl-based ASM-OSCs. The acceptor FO-2Cl, by introducing two oxygen atoms into the backbone of F-2Cl, exhibits red-shifted absorption, enhanced crystallinity, and improved electron mobility compared with F-2Cl. When using a small-molecule C8-C-F as the donor, the ASM-OSCs of F-2Cl- and FO-2Cl showed low power conversion efficiencies (PCEs) of 5.17 and 0.64%, respectively. However, with TA treatment, the PCEs of F-2Cl- and FO-2Cl-based devices were significantly improved to 12.15 and 13.91%, respectively. It was revealed that the TA treatment could effectively tune the phase separation of the active layer morphology with the interpenetrating network and contribute to the enhanced efficiency. Additionally, with TA treatment, the blend of C8-C-F:FO-2Cl demonstrated more favorable phase separation with higher crystallinity and stronger molecular packing compared with that of C8-C-F:F-2Cl. The results demonstrate that the phase separation of ASM-OSCs can be effectively tuned by TA treatment in combination with the delicate molecular design.