In organic donor-acceptor systems, ultrafast interfacial charge transfer (CT), charge separation (CS), and charge recombination (CR) are key determinants of the overall performance of photovoltaic devices. However, a profound understanding of these photophysical processes at device interfaces remains superficial, creating a major bottleneck that circumvents advancements and the optimization of these solar cells. Here, results from time-resolved laser spectroscopy and high-resolution electron microscopy are examined to provide the fundamental information necessary to fabricate and optimize organic solar cell devices. In real time, CT and CS are monitored at the interface between three fullerene acceptors (FAs) (PC71BM, PC61BM, and IC60BA) and the PTB7-Th donor polymer. Femtosecond transient absorption (fs-TA) data demonstrates that photoinduced electron transfer from the PTB7-Th polymer to each FA occurs on the sub-picosecond time scale, leading to the formation of long-lived radical ions. It is also found that the power conversion efficiency improves from 2% in IC60BA-based solar cells to >9% in PC71BM-based devices, in support of our time-resolved results. The insights reported in this manuscript provide a clear understanding of the key variables involved at the device interface, paving the way for the exploitation of efficient CS and subsequently improving the photoconversion efficiency. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.