In 2009, Kojima et al. introduced a perovskite solar cell delivering 3.8% power conversion efficiency (PCE). Then, in 2012, Henry Snaith’s group demonstrated a solution-processed perovskite solar cell with a PCE of 10.9%. Ever since, a race for the highest PCE perovskite solar cells has taken over the photovoltaic research community with the latest confirmed maximum PCE, as of 2020, at 25.2%. However, to be realistically viable, perovskites need to overcome their problem with long-term stability. Numerous studies, both theoretical and experimental, have tackled the issue. Some involved looking solely at the effects of humidity, temperature or oxygen on the active layer, whereas others focused on the effects of UV light on the solar cell structure. These single factor studies provide invaluable insights on the degradation of perovskites. Yet, a more holistic approach is needed to understand the effects of salient primary factors along with confounding higher order factors on the degradation. The design of experiment (DOE) methodology is uniquely suited for this endeavor. Few studies have employed a multifactorial approach in perovskite investigations. In this work, we seek to provide a mechanistic understanding of the degradation of perovskite solar cells in operation by focusing on methylammonium lead triiodide (CH₃NH₃PbI₃ or MAPbI₃) and tracking over time its crystallographic (XRD), optical (UV-Vis), and electrical (IV) characteristics under various electric load and temperature conditions. Moreover, we also record the evolution of electronic defects via Photo-Induced Current Transient Spectroscopy (PICTS). Using these techniques, we found that two interaction factors (temperature × load & temperature × time) were significant in the degradation of the perovskite cells studied, which validates the importance of our holistic approach. Furthermore, we found that bands of trap states, initially highly localized deep within the band gap of the perovskite, widened over the exposure period and increasing temperature. We also found that the average trap activation energy for each band of trap states became shallower over the degradation period. These observations establish a mechanistic link between deep level traps and the evolution of the current-voltage characteristics, crystallite size, microstrain, and optical absorption.