We provide a comprehensive description of the defect tolerance of sodium-borosilicate glasses upon sharp contact loading. This is motivated by the key role which is taken by this particular glass system in a wide variety of applications, ranging from electronic substrates, display covers and substrates for biomedical imaging and sensing to, e.g., radioactive waste vitrification. The present report covers the mechanical properties of glasses in the Na2O–B2O3–SiO2 ternary over the broad range of compositions from pure SiO2 to binary sodium-borates, and crossing the regions of various commercially relevant specialty borosilicate glasses, such as the multi-component Duran-, Pyrex- and BK7-type compositions and typical soda-lime silicate glasses, which are also included in this study. In terms of structure, the considered glasses may be separated into two groups, that is, one series which contains only bridging oxygen atoms, and another series which is designed with an increasing number of non-bridging oxygen ions. Elastic moduli, Poisson ratio, hardness as well as creep and crack resistance were evaluated, as well as the contribution of densification to the overall amount of indentation deformation. Correlations between the mechanical properties and structural characteristics of near- and mid-range order are discussed, from which we obtain a mechanistic view at the molecular reactions which govern the overall deformation reaction and, ultimately, contact cracking.