The growing nuclear threat has amplified the need for developing diverse and accurate nuclear forensics analysis techniques to strengthen nuclear security measures. The work presented here is part of a research effort focused on developing a methodology for reactor-type discrimination of weapons-grade plutonium. To verify the developed methodology, natural UO2 fuel samples were irradiated in a thermal neutron spectrum at the University of Missouri Research Reactor (MURR) and produced approximately 20 μg of weapons-grade plutonium test material. Radiation transport simulations of common thermal reactor types that can produce weapons-grade plutonium were performed, and the results are presented here. These simulations were needed to verify whether the plutonium produced in the natural UO2 fuel samples during the experimental irradiation at MURR was a suitable representative to plutonium produced in common thermal reactor types. Also presented are comparisons of fission product and plutonium concentrations obtained from computational simulations of the experimental irradiation at MURR to the nondestructive and destructive measurements of the irradiated natural UO2 fuel samples. Gamma spectroscopy measurements of radioactive fission products were mostly within 10%, mass spectroscopy measurements of the total plutonium mass were within 4%, and mass spectroscopy measurements of stable fission products were mostly within 5%.