We investigate the photodegradation in inert atmosphere of (poly 3-hexylthiophene:[6,6]-phenyl-C61-butyric acid methyl ester) (P3HT:PCBM) heterojunction solar cells under continuous illumination using advanced electrical characterization and a device modeling tool. Our results indicate that different failure mechanisms contribute to the performance loss. The first 250 h of illumination induced p-type doping and recombination related to traps in the blend which mainly decreases the short-circuit current and the efficiency of the cells. Device modeling and simulation allowed us to prove that increased p-type doping of the blend provoke the loss in the short-circuit current and the quantum efficiency by simultaneous reduction of charge carrier mobility and the electric field together with a shrink of the space charge region. Transmission electron microscopy (TEM) measurements reveal a change in the blend morphology upon long illumination times manifested by phase segregation in the blend. The reduction in the open-circuit voltage is reported to be related to a slight reduction of the charge transfer energy (CT) upon 700 h of illumination aging. The final failure mechanism was a rapid drop in the fill factor which occurs upon 1000 h of illumination and manifested by the appearance of an S-shape J–V characteristic. This failure mechanism is linked to the reduction of charge extraction caused by a reduced surface recombination velocity at the contacts.