Metallic glasses (MGs) exhibit greater elastic limit and stronger resistance to plastic deformation than their crystalline metal counterparts. Their capacity to withstand plastic straining is further enhanced at submicrometer length scales. For a range of microelectromechanical applications, the resistance of MGs to damage and cracking from thermal and mechanical stress or strain cycling under partial or complete constraint is of considerable scientific and technological interest. However, to our knowledge, no realtime, high-resolution transmission electron microscopy observations are available of crystallization, damage, and failure from the controlled imposition of cyclic strains or displacements in any metallic glass. Here we present the results of a unique in situ study, inside a high-resolution transmission electron microscope, of glassto-crystal formation and fatigue of an Al-based MG. We demonstrate that cyclic straining progressively leads to nanoscale surface roughening in the highly deformed region of the starter notch, causing crack nucleation and formation of nanocrystals. The growth of these nanograins during cyclic straining impedes subsequent crack growth by bridging the crack. In distinct contrast to this fatigue behavior, only distributed nucleation of smaller nanocrystals is observed with no surface roughening under monotonic deformation. We further show through molecular dynamics simulation that these findings can be rationalized by the accumulation of strain-induced nonaffine atomic rearrangements that effectively enhances diffusion through random walk during repeated strain cycling. The present results thus provide unique insights into fundamental mechanisms of fatigue of MGs that would help shape strategies for material design and engineering applications.fatigue crack initiation | fatigue crack growth | fracture | shear diffusion transformation zone M etallic glasses (MGs) possess several unique physical properties, including greater elastic limit and stronger resistance to plastic deformation, compared with crystalline metals and alloys (1-7). For a range of microelectromechanical applications (1, 7-12), the damage tolerance and crack resistance of MGs from thermal and mechanical stress or strain cycling under partial or complete constraint is of significant scientific and technological interest (13-18). Bulk MGs can undergo fully reversible elastic deformation to a strain limit of about 2%, more than an order of magnitude greater than that of coarse-grained crystalline metals, whereupon inelastic deformation commences at stress levels on the order of gigapascals (1, 2). Such high strength, however, is often accompanied by very limited ductility at room temperature. Experiments on MGs in thin-film form or as small-volume structures (typically hundreds of nanometers in linear dimensions) reveal that their elastic strain limit and corresponding strength are further enhanced, to values double those of bulk MGs (7-9). These findings suggest opportunities to use MGs in micro-and nanoscale syst...