Creating vacancy is often highly effective in enhancing the hydrogen evolution performance of transition metal-based catalysts. Vacancy-rich Ni nanosheets have been fabricated via topochemical formation of two-dimentional (2D) Ni2B on graphene precursor followed by boron leaching. Anchored on graphene, a few atomic layered Ni2B nanosheets are first obtained by reduction and annealing. Large number of atomic vacancies are then generated in the Ni2B layer via leaching boron atoms. When used for hydrogen evolution reaction (HER), the vacancy-rich Ni/Ni(OH)2 heterostructure nanosheets demonstrate remarkable performance with a low overpotential of 159 mV at a current density of 10 mA·cm−2 in alkaline solution, a dramatic improvement over 262 mV of its precursor. This enhancement is associated with the formation of vacancies which introduce more active sites for HER along Ni/Ni(OH)2 heterointerfaces. This work offers a facile and universal route to introduce vacancies and improve catalytic activity. [Figure not available: see fulltext.]