The synthesis of 2D layered double hydroxides (LDHs) monolayer remains a major challenge for energy conversion and storage. Herein, a one-pot strategy is reported to synthesize nitrate-intercalated nickel–iron LDHs (NiFe LDHs_NO₃⁻) by using hexamethylenetetramine as a hydrolysis reagent. The NiFe LDHs monolayers can be facilely dispersed in water within 10 s by hand shaking because the NiFe LDHs_NO₃⁻ bulk owns an enlarged interlayer spacing up to 8.2 Å. Critical information on the structure, prerequisite, and universality of this strategy is obtained by advanced characterization methods, for example, transmission electron microscopy, atomic force microscopy, X-ray diffraction pattern, Fourier-transform infrared spectroscopy, and X-ray photoelectron spectroscopy. As a proof of concept application, the NiFe LDHs monolayer is employed as an electrocatalyst for oxygen evolution reaction and displays much superior performance to the bulk LDHs and RuO₂. This facile strategy paves the way for designing other LDHs monolayers for highly active electrocatalysts.