This article demonstrates improvements in the operational stability of organic solar cells (OSCs) by taking advantage of the relationship between oxygen stoichiometry and conductivity in nanostructured metal oxide semiconductors (n-MOS). OSCs in the inverted device configuration of ITO/Ca/P3HT:PCBM/MoO3/Ag were employed in the present study. A high degree of oxygen defects were introduced in the hole-conducting MoO3 layer by annealing the devices under vacuum (≥10−5 mbar) for nominal temperature (120 °C) and time (10 min). The above devices had much higher operational stability, when tested following the ISOS-D-1 (shelf) protocol, than control devices annealed conventionally, i.e., in nitrogen atmosphere. Employing current–voltage measurement as functions of temperature and photon flux, we show that the devices annealed under vacuum have a lesser density of traps than those annealed in nitrogen. The lesser trap density is shown to be beneficial in reducing the rate of electron recombination thereby increasing the operational stability of the corresponding device. A number of experiments were undertaken to show that the difference in the operation stability of the device results from the difference in conductivity of the nanostructured MoO3 hole transporting layer. The charge extraction by linear increasing voltage spectroscopy shows that charges are relaxed at the trap states in the device annealed in nitrogen whereas they are efficiently transported in the other device. We identify that building up of an interfacial potential barrier as a result of the charge relaxation at the trap states and the corresponding chemical changes in the devices annealed conventionally is the source of degradation of the device performance over time. To our knowledge, this is the first report that successfully overcomes hole-conductivity induced degradation in organic solar cells.