Controlling thin film morphology is key in optimizing the efficiency of polymer-based photovoltaic (PV) devices. We show that morphology and interfacial behavior of the multicomponent active layers confined between electrodes are strongly influenced by the preparation conditions. Here, we provide detailed descriptions of the morphologies and interfacial behavior in thin film mixtures of regioregular poly(3-hexylthiophene) (P3HT) and [6,6]-phenyl C61-butyric acid methyl ester (PCBM), a typical active layer in a polymer-based PV device, in contact with an anode layer of PEDOT-PSS and either unconfined or confined by an Al cathode during thermal treatment. Small angle neutron scattering and electron microscopy show that a nanoscopic, bicontinuous morphology develops within seconds of annealing at 150 °C and coarsens slightly with further annealing. P3HT and PCBM are shown to be highly miscible, to exhibit a rapid, unusual interdiffusion, and to display a preferential segregation of one component to the electrode interfaces. The ultimate morphology is related to device efficiency.