The lithiation reaction of single ZnO nanowire (NW) electrode in a Li-ion nanobattery configuration was observed by in situ transmission electron microscopy. Upon first charge, the single-crystalline NW was transformed into a nanoglass with multiple glassy nanodomains (Gleiter, H. MRS Bulletin2009, 34, 456) by an intriguing reaction mechanism. First, partial lithiation of crystalline NW induced multiple nanocracks ∼70 nm ahead of the main lithiation front, which traversed the NW cross-section and divided the NW into multiple segments. This was followed by rapid surface diffusion of Li(+) and solid-state amorphization along the open crack surfaces. Finally the crack surfaces merged, leaving behind a glass-glass interface (GGI). Such reaction front instability also repeated in the interior of each divided segment, further subdividing the NW into different nanoglass domains (nanoamorphization). Instead of the profuse dislocation plasticity seen in SnO(2) NWs (Science2010, 330, 1515), no dislocation was seen and the aforementioned nanocracking was the main precursor to the electrochemically driven solid-state amorphization in ZnO. Ab initio tensile decohesion calculations verified dramatic lithium embrittlement effect in ZnO, but not in SnO(2). This is attributed to the aliovalency of Sn cation (Sn(IV), Sn(II)) in contrast to the electronically more rigid Zn(II) cation.