The power conversion efficiencies (PCEs) of organic solar cells (OSCs) have surpassed 19% thanks to the innovation of polymer donors and molecular acceptors. However, the batch-to-batch variations in polymer materials are detrimental to the reproducibility of the device performance. In comparison, small-molecule donors (SMDs) possess some unique advantages, such as well-defined molecular weights, easy purification, and excellent batch-to-batch repeatability. Herein, a pair of regioisomeric SMDs (BT-O1 and BT-O2) has been synthesized with alkoxy groups as S center dot center dot center dot O noncovalently conformational locks (NoCLs) at the inner and outer position, respectively. Theoretical and experimental results reveal that the regioisomeric effect has a significant influence on the light-harvest ability, energy levels, molecular geometries, internal reorganization energy, and packing behaviors for the two SMDs. As a result, BT-O2-based binary device shows an impressive PCE of 13.99%, much higher than that of BT-O1 based one (4.07%), due to the better-aligned energy level, more balanced charge transport, less charge recombination, lower energy loss, and more favorable phase separation. Furthermore, the fullerene derivative PC71BM is introduced into BT-O2:H3 as the third component to achieve a notable PCE of 15.34% (certified 14.6%). Overall, this work reveals that NoCLs is a promising strategy to achieve high-performance SMDs for all-small-molecule OSCs.