Despite numerous organic semiconductors being developed during the past decade, C-70 derivatives are predominantly used as electron acceptors in efficient polymer solar cells (PSCs). However, as-prepared C-70 mono-adducts intrinsically comprise regioisomers that would mask individual device performances depending on the substituent position on C-70. Herein, we separate the regioisomers of C-70 monoadducts for PSC applications for the first time. Systematic investigations of the substituent position effect using a novel symmetric C-70 mono-adduct ([70] NCMA) and a prevalent, high-performance one ([70] PCBM) reveals that we can control the structures of the blend films with conjugated polymers and thereby improve the PSC performances by regioisomer separation. Our approach demonstrates the significance of exploring the best-matching regioisomer of C-70 mono-adducts with high-performance conjugated polymers, which would achieve a remarkable progress in PSC devices.