To increase the commercialization of fuel cell electric vehicles, it is imperative to improve the activity and performance of electrocatalysts through combined efforts focused on material characterization and device-level integration. Obtaining fundamental insights into the ongoing structural and compositional changes of electrocatalysts is crucial for not only transitioning an electrode from its as-prepared to functional state, also known as 'conditioning', but also for establishing intrinsic electrochemical performances. Here, we investigated several oxygen reduction reaction (ORR) electrocatalysts via in situ and ex situ characterization techniques to provide fundamental insights into the interfacial phenomena that enable peak ORR mass activity and high current density performance. A mechanistic understanding of a fuel cell conditioning procedure is described, which encompasses voltage cycling and subsequent voltage recovery (VR) steps at low potential. In particular, ex situ membrane electrode assembly characterization using transmission electron microscopy and ultra-small angle X-ray scattering were performed to determine changes in carbon and Pt particle size and morphology, while in situ electrochemical diagnostics were performed either during or after specific points in the testing protocol to determine the electrochemical and interfacial changes occurring on the catalyst surface responsible for oxygen transport resistances through ionomer films. The results demonstrate that the voltage cycling (break-in) step aids in the removal of sulfate and fluoride and concomitantly reduces non-Fickian oxygen transport resistances, especially for catalysts where Pt is located within the pores of the carbon support. Subsequent low voltage holds at low temperature and oversaturated conditions, i.e., VR cycles, serve to improve mass activities by a factor of two to three, through a combined removal of contaminants, surface-blocking species (e.g., oxides), and rearrangement of the catalyst atomic structure (e.g., Pt-Pt and Pt-Co coordination).