Central π‐core engineering of non‐fullerene small molecule acceptors (NF‐SMAs) is effective in boosting the performance of organic solar cells (OSCs). Especially, selenium (Se) functionalization of NF‐SMAs is considered a promising strategy but the structure‐performance relationship remains unclear. Here, we synthesize two isomeric alkylphenyl‐substituted selenopheno3,2‐bthiophene‐based NF‐SMAs named mPh4F‐TS and mPh4F‐ST with different substitution positions, and contrast them with the thieno3,2‐bthiophene‐based analogue, mPh4F‐TT. When placing Se atoms at the outer positions of the π‐core, mPh4F‐TS shows the most red‐shifted absorption and compact molecular stacking. The PM6 : mPh4F‐TS devices exhibit excellent absorption, high charge carrier mobility, and reduced energy loss. Consequently, PM6 : mPh4F‐TS achieves more balanced photovoltaic parameters and yields an efficiency of 18.05 %, which highlights that precisely manipulating selenium functionalization is a practicable way toward high‐efficiency OSCs. Two region‐specific selenium‐based non‐fullerene acceptors flanking conjugated side chains are compared with their sulfur‐based analogue. mPh4F‐TS with selenium at the outer positions show the most rigid skeleton, red‐shifted absorption and compact stacking. The PM6 : mPh4F‐TS organic solar cells exhibit the lowest energetic disorders, the highest charge carrier mobility and the best photon response, affording a top‐ranking efficiency of >18 %.