How different integrins that bind to the same type of extracellular matrix protein mediate specific functions is unclear. We report the functional analysis of β₁- and α_v-class integrins expressed in pan-integrin-null fibroblasts seeded on fibronectin. Reconstitution with β₁-class integrins promotes myosin-II-independent formation of small peripheral adhesions and cell protrusions, whereas expression of α_v-class integrins induces the formation of large focal adhesions. Co-expression of both integrin classes leads to full myosin activation and traction-force development on stiff fibronectin-coated substrates, with α_v-class integrins accumulating in adhesion areas exposed to high traction forces. Quantitative proteomics linked α_v-class integrins to a GEF-H1–RhoA pathway coupled to the formin mDia1 but not myosin II, and α₅β₁ integrins to a RhoA–Rock–myosin II pathway. Our study assigns specific functions to distinct fibronectin-binding integrins, demonstrating that α₅β₁integrins accomplish force generation, whereas α_v-class integrins mediate the structural adaptations to forces, which cooperatively enable cells to sense the rigidity of fibronectin-based microenvironments.