NiFe layered double hydroxides (LDHs) are among the most active electrocatalysts for alkaline oxygen evolution reaction (OER) and OER selective seawater oxidation. These promising applications call for a fundamental understanding of the catalyst/electrolyte interaction, which is challenging to investigate during operation conditions. This work reports an operando structure–reactivity analysis of NiFe LDH as the electrocatalyst for the OER in alkaline and alkalinized NaCl electrolytes, by combining operando wide-angle X-ray scattering (WAXS) and electrochemical characterization. The operando results showed that higher pH values lead to a higher percentage of the OER active γ-NiFe LDH in the composition of the catalyst layer, larger Ni redox peaks, and higher OER activity. The addition of 0.5 M NaCl to moderate alkaline electrolytes (0.1–0.5 M KOH) also leads to larger Ni redox features and higher activity but appears to limit the percentage of γ-NiFe LDH during the OER in comparison to the corresponding NaCl-free electrolytes. Interestingly, a higher KOH concentration (1.0 M KOH, pH 14) could compensate this structural effect aligning the percentage of OER-active γ-NiFe LDH in both NaCl-free and NaCl-containing electrolytes. Additional scan rate investigations showed a strong correlation of the electrochemical accessibility of NiFe LDH with its history, scan rate, and NaCl addition. In particular, the faster and more effective break-in process induced by NaCl addition is proposed as the origin of the enhanced activity at low pH, despite the lower γ-phase percentage.