To fulfil their function, epithelial tissues need to sustain mechanical stresses and avoid rupture. Although rupture is usually undesired, it is central to some developmental processes, for example, blastocoel formation. Nonetheless, little is known about tissue rupture because it is a multiscale phenomenon that necessitates comprehension of the interplay between mechanical forces and biological processes at the molecular and cellular scales. Here we characterize rupture in epithelial monolayers using mechanical measurements, live imaging and computational modelling. We show that despite consisting of only a single layer of cells, monolayers can withstand surprisingly large deformations, often accommodating several-fold increases in their length before rupture. At large deformation, epithelia increase their stiffness multiple fold in a process controlled by a supracellular network of keratin filaments. Perturbing the keratin network organization fragilized the monolayers and prevented strain-stiffening. Although the kinetics of adhesive bond rupture ultimately control tissue strength, tissue rheology and the history of deformation set the strain and stress at the onset of fracture.