High-energy photons from medical accelerators are used to treat tumors in cancer patients. One consequence is the production of neutrons from photonuclear interactions in the high-Z accelerator components. The release and capture of neutrons produce radioactive nuclei that can irradiate patients and medical personnel. The goal of this study is to develop a method for quantifying the activation of accelerator components using MCNPX. To benchmark this method, we took activation measurements from the irradiation of a series of zinc plates using a 55-MeV electron beam and compared them with MCNPX calculations. The measured cumulative photon-induced activity from 68Zn(,p)67Cu interactions in all of the plates was 10.8 MBq, which is in 5.4% agreement with the calculated value of 10.2 ± 1.1 MBq. Based on these results, a series of simulations were performed in order to optimize the photon- and neutron-induced activity in tungsten for subsequent experiments. The radioactivity from activated short-lived isotopes and subsequent buildup can be significant from repeated accelerator operations during a day. The approach described in this paper is useful in quantifying the origin and the amount of nuclear activation and the buildup of radioactivity.