We report on the mechanical and electrical response of VO2 nanowires during the application of uniaxial tensile strain at room temperature. Stress–strain curves exhibit plateaus, which are characteristic of reversible transformations. The mechanical data are also discussed in terms of size effects, which is important for applications where the structural integrity is key to the performance of devices. Electrical measurements during straining show a distinct increase in resistivity at the M1–M2 transition, and a strong piezo-resistive effect for the M2 phase, disclosing new opportunities for future nanostructured devices. To our knowledge, this is the first time that piezoresistivity in the M2 phase has been reported.