An isomerism strategy was employed to develop single, end‐group bromine-substituted non‐fullerene two isomeric acceptors, 2,2′-((2Z,2′Z)-((12,13-bis(2-ethyl-hexyl)-3,9-diundecyl-12,13-dihydro-[1,2,5]thiadiazolo [3,4-e]thieno[2,"3′′:4′,5′] thieno[2′,3′:4,5]pyrrolo [3,2-g]thieno[2′,3′:4,5]thieno[3,2-b]indole-2,10-diyl) bis(methanylylidene))bis(4-bromo-3-oxo-2,3-dihydro-1H-inden-1-ylidene)dimalononitrile (BTIC-2Br-β) and 2,2′-((2Z,2′Z)-((12,13-bis(2-ethylhexyl)-3,9-diun-decyl-12,13-dihydro-[1,2,5]thiadiazolo[3,4-e]thieno [2,"3′′:4′,5′] thieno[2′,3′:4,5]pyrrolo[3,2-g]thieno [2′,3′:4,5]thieno[3,2-b]indole-2,10-diyl)bis(metha-nylylidene))bis(5-bromo-3-oxo-2,3-dihydro-1Hinden-1-ylidene)dimalononitrile (BTIC-2Br-γ), for organic solar cells, aimed to examine the improvement of power conversion efficiency (PCE). The effects of isomerism on their optical, electronic, charge dynamics, morphological, and photovoltaic properties were systematically investigated. When blended with a donor poly{[4,8-bis[5-(2-ethylhexyl)-4-fluoro-2-thienyl]benzo[1,2-b:4,5-b′]dithiophene-2,6-diyl]-alt-[2,5-thiophenediyl[5,7-bis(2-ethylhexyl)-4,8-dioxo-4H,8H-benzo[1,2-c:4,5-c′]dithiophene-1,3-diyl]]} (PBDB-TF), BTIC-2Br-γ-based devices exhibited an outstanding PCE of 16.52%, they exhibited an outstanding PCE of 16.52%, which was the highest recorded value among brominated acceptors, compared with 8.11% obtained for BTIC-2Br-βbased devices. Crystallographic analysis of BTIC-2Brγ single-crystal demonstrated that the entire molecular backbone presented a plane structure between the core and end groups. Moreover, multiple intermolecular interactions such as Br⋯π and CN⋯H existing in the solid-state allowed BTIC-2Br-γ to form a three-dimensional (3D) network-packing structure, providing more electron transport channels. Our morphology investigations revealed that the BTIC-2Br-γblend films displayed tailored crystallite with distinct fibrillary nanostructures, and the low miscibility of PBDB-TF and BTIC-2Br-γ obtained by the contact angle could assist the formation of the fibrillary interpenetrating networks to achieve effective charge transport pathways. Compared with BTIC-2Br-β, BTIC-2Br-γ possessed a higher extinction coefficient, more balanced charge transport, and weaker bimolecular recombination. This work shows that subtle changes in bromine position can significantly improve the photovoltaic efficiencies of organic solar cells (OSCs); therefore, it provides a new guideline for the rational design of efficient fused-ring electron acceptors (FREAs).