A key challenge in today’s fuel cell research is the understanding and maintaining the durability of the structure and performance of initially highly active Pt fuel cell electrocatalysts, such as dealloyed Pt or Pt monolayer catalysts. Here, we present a comparative long-term stability and activity study of supported dealloyed PtCu3 and PtCo3 nanoparticle fuel cell catalysts for the oxygen reduction reaction (ORR) and benchmark them to a commercial Pt catalyst. PtCu3 and PtCo3 were subjected to two distinctly different voltage cycling tests: the “lifetime” regime [10 000 cycles, 0.5–1.0 V vs. RHE (reversible hydrogen electrode), 50 mV s−1] and the corrosive “start-up” regime (2000 cycles, 0.5–1.5 V vs. RHE, 50 mV s−1). Our results highlight significant activity and stability benefits of dealloyed PtCu3 and PtCo3 for the ORR compared with those of pure Pt. In particular, after testing in the “lifetime” regime, the Pt-surface-area-based activity of the Pt alloy catalysts is still two times higher than that of pure Pt. From our electrochemical, morphological, and compositional results, we provide a general picture of the temporal sequence of dominant degradation mechanisms of a Pt alloy catalyst during its life cycle.