Electrocatalysts featuring high activity, selectivity and stability are urgently needed in solar-electricity powered energy-conversion technologies. In the past decade, various electrocatalysts have been demonstrated to be electrocatalytically active toward the hydrogen evolution reaction (HER) and oxygen evolution reaction (OER). Despite the significant progress, catalyst discovery is still dominated by “trial-and-error” practice due to the lack of understanding of the origin of electrocatalytic activity, active site structures and key factors determining the operando electrocatalytic performance. Therefore, this critical review focuses on summarizing effective catalyst activation strategies to enable efficient catalyst discovery, on the basis of understanding real active sites for the HER and OER. Meanwhile, theory prediction and operando characterization techniques have also been introduced to identify the origin of electrocatalytic activity and active site structures. Moreover, catalyst atomic structure reconstruction/rearrangement under working conditions and the accompanying catalyst activation strategies have been discussed to address the negative impacts of reaction media. Finally, a brief perspective on the challenges and future directions for predicting, characterizing and understanding operando active sites to discover efficient activation strategies will also be presented.