The development of organic transistors for flexible electronics requires the understanding of device behavior upon the application of strain. Here, a comprehensive study of the effect of polymer-dielectric and semiconductor chemical structure on the device performance under applied strain is reported. The systematic change of the polymer dielectric results in the modulation of the effects of strain on the mobility of organic field-effect transistor devices. A general method is demonstrated to lower the effects of strain in devices by covalent substitution of the dielectric surface. Additionally, the introduction of a hexyl chain at the peripheries of the organic semiconductor structure results in an inversion of the effects of strain on device mobility. This novel behavior may be explained by the capacitative coupling of the surface energy variations during applied strain.