Two-dimensional (2D) (hydro)oxide materials, that is, nanosheets, enable the preparation of advanced 2D materials and devices. The general synthesis route of nanosheets involves exfoliating layered metal (hydro)oxide crystals. This exfoliation process is considered to be time-consuming, hindering their industrial-scale production. Based on in situ exfoliation studies on the protonated layered titanate H1.07Ti1.73O4⋅H2O (HTO), it is now shown that ion intercalation-assisted exfoliation driven by chemical reaction provides a viable and fast route to isolated nanosheets. Contrary to the general expectation, data indicate that direct exfoliation of HTO occurs within seconds after mixing of the reactants, instead of proceeding via a swollen state as previously thought. These findings reveal that ion intercalation-assisted exfoliation driven by chemical reaction is a promising exfoliation route for large-scale synthesis.