Binding of the surface protein clumping factor A (ClfA) to endothelial cell integrin αβ plays a crucial role during sepsis, by causing endothelial cell apoptosis and loss of barrier integrity. ClfA uses the blood plasma protein fibrinogen (Fg) to bind to αβ but how this is achieved at the molecular level is not known. Here we investigate the mechanical strength of the three-component ClfA-Fg-αβ interaction on living bacteria, by means of single-molecule experiments. We find that the ClfA-Fg-αβ ternary complex is extremely stable, being able to sustain forces (∼800 pN) that are much stronger than those of classical bonds between integrins and the Arg-Gly-Asp (RGD) tripeptide sequence (∼100 pN). Adhesion forces between single bacteria and αβ are strongly inhibited by an anti-αβ antibody, the RGD peptide, and the cyclic RGD peptide cilengitide, showing that formation of the complex involves RGD-dependent binding sites and can be efficiently inhibited by αβ blockers. Collectively, our experiments favor a binding mechanism involving the extraordinary elasticity of Fg. In the absence of mechanical stress, RGD sequences in the Aα chains mediate weak binding to αβ, whereas under high mechanical stress exposure of cryptic Aα chain RGD sequences leads to extremely strong binding to the integrin. Our results identify an unexpected and previously undescribed force-dependent binding mechanism between ClfA and αβ on endothelial cells, which could represent a potential target to fight staphylococcal bloodstream infections.