Transition-metal　oxides　constitute　an　important　family　of　high-capacity　anodes　for　Li-ion　batteries.　ZnO　is　a　model　material　due　to　the　high　theoretical　capacity　and　its　representative　reaction　mechanism　upon　lithiation.　We　investigate　the　structural　evolution,　mechanical　degradation,　and　stress-regulated　electrochemical　reactions　of　ZnO　nanowires　during　the　first　lithiation　through　coordinated　in-situ　transmission　electron　microcopy　experiments,　continuum　theories,　and　first-principles　computation.　Lithiation　induces　a　field　of　stress　in　ZnO　nanowires.　The　stress　field　mediates　the　electrochemical　reaction　and　breaks　the　planar　solid-state　reaction　front　into　a　curved　interface.　The　tensile　stress　in　the　lithiated　shell　causes　surface　fracture　in　the　basal　plane　of　nanowires.　The　compressive　stress　in　the　unlithiated　core　retards　local　reactions　and　results　in　an　uneven　lithiation　on　a　given　basal　plane.　We　also　observe　that　metallic　Zn　nanoparticles　aggregate　in　the　amorphous　matrix　of　the　reaction　products.　At　a　critical　size,　Zn　nanoparticles　impede　the　propagation　of　the　reaction　front　due　to　the　thermodynamically　unfavorable　lithiation　reaction.　The　results　provide　fundamental　perspectives　on　the　chemomechanical　behaviors　of　oxides　for　the　next-generation　Li-ion　batteries.　©　2015　Elsevier　Ltd.　All　rights　reserved.