Side chain engineering is an efficient strategy for modifying molecular properties and regulating active layer morphologies, thus improving the performance of organic solar cells (OSCs). Here, we design two acceptors, namely FEH2C8-2Cl and F3EH-2Cl, based on an acceptor F-2Cl by introducing isomerized side chains on the molecular backbones. Film absorptions, energy levels and packing behaviors of the three isomer acceptors show a considerable difference with the isomer side chains. Using PM6 as a donor, the FEH2C8-2Cl-based device affords the best power conversion efficiency (PCE) of 14.60% with a high fill factor of 79.04% owing to the more favorable active layer morphology. Moreover, the device based on FEH2C8-2Cl shows good active layer thickness tolerance with an efficiency of 12.14% at a thickness of 300 nm, which is favored for the fabrication of large area OSCs. Finally, a large area module fabricated with PM6:FEH2C8-2Cl as the active layer shows a PCE of 11.71% with an area of 25 cm(2).