With the continuous transistor scaling, device mismatch related to intrinsic process variability increases and becomes one of the most important problems to be faced during circuit design. In addition, gate oxide wear-out strongly affects the device reliability and adds a time dependence to device mismatch. In this paper, the impact on circuit functionality of both process variability and gate oxide degradation is studied. First, the effect of the gate oxide damage on the NMOS and PMOS transistor characteristics and their variability has been analyzed. Second, a methodology based on combined SPICE and Monte Carlo simulations to analyze the time-dependent variability at device and circuit levels is presented, which has allowed to reproduce the experimental data. Finally, using the proposed methodology, the influence of the process variability and gate oxide wear-out on the functionality of different configurations of an amplifier circuit was investigated. The results show that both aspects can be decisive in the circuit reliability.