Due to their extraordinary scientific significance and technological importance, inorganic single crystals with highly reactive surfaces have long been targeted. Unfortunately, surfaces with high reactivity usually diminish rapidly during the crystal growth process as a result of the minimization of surface energy. A typical example is titanium dioxide (TiO₂), which has promising energy and environmental applications. Most available anatase TiO₂ crystals are mainly dominated by the thermodynamically stable {101} facets (more than 94% according to Wulff construction), as opposed to the much more reactive {001} facets. Here, we demonstrate that for fluoride-terminated surfaces this stability is reversed - {001} surfaces are energetically preferable to {101}. We explored this effect systematically for a range of non-metallic atoms (H, B, C, N, O, F, Si, P, S, Cl, Br, I) by first-principle quantum chemical calculations. Based on this theoretical prediction, we have synthesized uniform anatase TiO₂ single crystals with a high percentage (47%) of {001} facets by using hydrofluoric acid (HF) as morphology controlling agent. Moreover, high quality anatase TiO₂ single crystal nanosheets mainly enclosed by {001} facets (61%) have also been prepared, which is based on the synergistic functions of chemisorbed F to lower the surface energy and 2-propanol to act as protective capping agent. With the well-defined anatase single crystals reported in this communication, it may be practical to study the functions (i.e., photocatalysis) of high-reactive {001} facets of anatase more accurately after surface activation.