Modeling predictions and experimental measurements were obtained to characterize the electro-mechanical response of radio frequency (RF) microelectromechanical (MEM) switches due to variations in surface roughness and finite asperity deformations. Three-dimensional surface roughness profiles were generated, based on a Weierstrass–Mandelbrot fractal representation, to match the measured roughness characteristics of contact bumps of manufactured RF MEMS switches. Contact asperity deformations due to applied contact pressures were then obtained by a creep constitutive formulation. The contact pressure is derived from the interrelated effects of roughness characteristics, material hardening and softening, temperature increases due to Joule heating and contact forces. This modeling framework was used to understand how contact resistance evolves due to changes in the real contact area, the number of asperities in contact, and the temperature and resistivity profiles at the contact points. The numerical predictions were qualitatively consistent with the experimental measurements and observations of how contact resistance evolves as a function of deformation time history. This study provides a framework that is based on integrated modeling and experimental measurements, which can be used in the design of reliable RF MEMS devices with extended life cycles.