In this work, we developed the PM6:Y6‐based inverted structure organic photovoltaic (i‐OPV) with improved power conversion efficiency (PCE) and long‐term stability by resolving the origins of the performance deterioration. The deep defects between the metal oxide‐based electron transport layer and bulk‐heterojunction photoactive layer interface were responsible for suboptimal PCE and facilitated degradation of devices. While the density of deep traps is increased during the storage of i‐OPV, the penetrative oxygen‐containing defects additionally generated shallow traps below the band‐edge of Y6, causing an additional loss in the open‐circuit voltage. The suppression of interfacial defects by chemical modification effectively improved the PCE and long‐term stability of i‐OPV. The modified i‐OPV (mi‐OPV) achieved a PCE of 17.42%, which is the highest value among the reported PM6:Y6‐based i‐OPV devices. Moreover, long‐term stability was significantly improved: ~90% and ~80% retention of its initial PCE after 1200 h of air storage and illumination, respectively.