One pair of isomers, centrosymmetric anti-Py-1 and axisymmetric syn-Py-2, was designed and synthesized with an acceptor-donor-acceptor (A-D-A) structure by choosing dithienocyclopentapyrene with four 4-hexylphenyl side chains as the D unit, and 2-(5,6-difluoro-3-oxo-2,3-dihydro-1H-inden-1-ylidene) malononitrile as the A unit. In-depth structure-property relationship studies revealed that the isomers have similar UV/Vis absorption, fluorescence emission, and energy levels but significant differences in molecular shape, polarity, and charge mobility. Solution-processed bulk-heterojunction (BHJ) small-molecule organic solar cells with Py-1 as the electron-acceptor material and PTB7-Th as the electron-donor material exhibit a power conversion efficiency (PCE) of 6.07 %, or 60 % higher than that of Py-2 (3.7 %), which could be mainly attributed to the higher and more balanced hole/electron mobilities and better phase separation of the Py-1-based active layer.